Short-chain fatty acid - A critical interfering factor for allergic diseases.
Chemico-biological interactions
Allergy is a growing global public health problem with a high socio-economic impact. The incidence of allergic diseases is increasing year by year, which has attracted more and more attention. In recent years, a number of epidemiological investigations and gut microbiota studies have shown that gut microbiota dysbiosis is associated with an increased prevalence of various allergic diseases, such as food allergy, asthma, allergic rhinitis, and atopic dermatitis. However, the underlying mechanisms are complex and have not been fully clarified. Metabolites are one of the main ways in which the gut microbiota functions. Short-chain fatty acids (SCFAs) are the main metabolites of intestinal flora fermentation and are beneficial to human health. Studies have shown that SCFAs play an important role in maintaining intestinal homeostasis and regulating immune responses by recognizing receptors and inhibiting histone deacetylases, and are key molecules involved in the occurrence and development of allergic diseases. In addition, research on the regulation of gut microbiota and the application of SCFAs in the treatment of allergic diseases is also emerging. This article reviews the clinical and experimental evidence on the correlation between SCFAs and allergic diseases and the potential mechanisms by which SCFAs regulate allergic diseases. Furthermore, SCFAs as therapeutic targets for allergic diseases are also summarized and prospected.
10.1016/j.cbi.2023.110739
Neonatal Gastrointestinal and Respiratory Microbiome in Cystic Fibrosis: Potential Interactions and Implications for Systemic Health.
Madan Juliette C
Clinical therapeutics
PURPOSE:The gastrointestinal microbiome plays a critical role in nutrition and metabolic and immune functions in infants and young children and has implications for lifelong health. Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) mutations in CF result in viscous mucous production, frequent exposure to antibiotics, and atypical colonization patterns, resulting in an evolving dysbiosis of the gastrointestinal and respiratory microsystems; dysbiosis in CF results in systemic inflammation, chronic infection, and dysregulation of immune function. Dysbiosis in both the respiratory system and gut contributes to undernutrition, growth failure, and long-term respiratory and systemic morbidity in infants and children with CF. Understanding the role that the gut and respiratory microbiome plays in health or disease progression in CF will afford opportunities to better identify interventions to affect clinical changes. METHODS:Summary was done of the pertinent literature in CF and the study of the microbiome and probiotics. FINDINGS:New studies have identified bacteria in the respiratory tract in CF that are typically members of the intestinal microbiota, and enteral exposures to breast milk and probiotics are associated with prolonged periods of respiratory stability in CF. IMPLICATIONS:Understanding the complex interactions between the CFTR mutations, microbial colonization, and mucosal and systemic immunity is of major importance to inform new treatment strategies (such as restoring a healthier microbiome with probiotics or dietary interventions) to improve nutritional status and immune competence and to decrease morbidity and mortality in CF.
10.1016/j.clinthera.2016.02.008
[Correlation between Gut Microbiota and Lung Cancer].
Teng Jun,Zhao Yanfen,Jiang Yunning,Wang Qi,Zhang Yongsheng
Zhongguo fei ai za zhi = Chinese journal of lung cancer
Gene-environment interactions underlie cancer susceptibility and progression. The human body is exposed to and affected by the microenvironment seiscasts of various microorganisms and their metabolites, such as the microenvironment of gut microbiota. The relative abundance of some intestinal microbes in lung cancer patients was significantly different from that in the control group. These studies suggest that gut microbiota may be associated with lung cancer through some ways. At the same time, gut microbiota is relatively manageable environmental variables compared to the external environment we are exposed to, as they are highly quantifiable and relatively stable in the individual. Just as some measures of diagnosis, intervention and treatment of lung cancer targeting gut microbiota have achieved some results in clinical practice. In this review, we mainly discuss the role of gut microbiota and its metabolites in the progression and treatment of lung cancer through certain ways, such as regulation of metabolism, inflammation, and immune response. Finally, based on current research progress, it is inferred that research on gut microbiota may be an effective approach to the precise and personalized medical treatment of lung cancer.
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10.3779/j.issn.1009-3419.2020.101.39
Impact of diet and the bacterial microbiome on the mucous barrier and immune disorders.
Alemao Charlotte A,Budden Kurtis F,Gomez Henry M,Rehman Saima F,Marshall Jacqueline E,Shukla Shakti D,Donovan Chantal,Forster Samuel C,Yang Ian A,Keely Simon,Mann Elizabeth R,El Omar Emad M,Belz Gabrielle T,Hansbro Philip M
Allergy
The prevalence of chronic immune and metabolic disorders is increasing rapidly. In particular, inflammatory bowel diseases, obesity, diabetes, asthma and chronic obstructive pulmonary disease have become major healthcare and economic burdens worldwide. Recent advances in microbiome research have led to significant discoveries of associative links between alterations in the microbiome and health, as well as these chronic supposedly noncommunicable, immune/metabolic disorders. Importantly, the interplay between diet, microbiome and the mucous barrier in these diseases has gained significant attention. Diet modulates the mucous barrier via alterations in gut microbiota, resulting in either disease onset/exacerbation due to a "poor" diet or protection against disease with a "healthy" diet. In addition, many mucosa-associated disorders possess a specific gut microbiome fingerprint associated with the composition of the mucous barrier, which is further influenced by host-microbiome and inter-microbial interactions, dietary choices, microbe immigration and antimicrobials. Our review focuses on the interactions of diet (macronutrients and micronutrients), gut microbiota and mucous barriers (gastrointestinal and respiratory tract) and their importance in the onset and/or progression of major immune/metabolic disorders. We also highlight the key mechanisms that could be targeted therapeutically to prevent and/or treat these disorders.
10.1111/all.14548
Gut microbiome interventions in human health and diseases.
Nie Pengqing,Li Zhiqiang,Wang Yimeng,Zhang Yubing,Zhao Mengna,Luo Jie,Du Shiming,Deng Zixin,Chen Jincao,Wang Yunfu,Chen Shi,Wang Lianrong
Medicinal research reviews
Ongoing studies have determined that the gut microbiota is a major factor influencing both health and disease. Host genetic factors and environmental factors contribute to differences in gut microbiota composition and function. Intestinal dysbiosis is a cause or a contributory cause for diseases in multiple body systems, ranging from the digestive system to the immune, cardiovascular, respiratory, and even nervous system. Investigation of pathogenesis has identified specific species or strains, bacterial genes, and metabolites that play roles in certain diseases and represent potential drug targets. As research progresses, gut microbiome-based diagnosis and therapy are proposed and applied, which might lead to considerable progress in precision medicine. We further discuss the limitations of current studies and potential solutions.
10.1002/med.21584
[How does COVID-19 affect intestinal microbiota?]
MMW Fortschritte der Medizin
BACKGROUND:There is a bidirectional interaction between the intestines and lungs, the so-called lung-intestinal axis. METHOD:The review article reports on studies that deal with a possible influence of the intestinal microbiota on the immune response to a SARS-CoV-2 infection. RESULTS AND CONCLUSIONS:Studies have shown that COVID-19 is accompanied by dysbiosis that persists even after successful virus conversion (negative PCR). One study found that the severity of COVID-19 is associated with the intestinal microbiota. A dysbiosis could thus favor the so-called cytokine storm. There is indication that pre- and probiotics could boost the immune response in both the guts and lungs.
10.1007/s15006-021-0200-5
Mechanisms of gastrointestinal barrier dysfunction in COVID-19 patients.
World journal of gastroenterology
Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major global public health event, resulting in a significant social and economic burden. Although COVID-19 was initially characterized as an upper respiratory and pulmonary infection, recent evidence suggests that it is a complex disease including gastrointestinal symptoms, such as diarrhea, nausea, and vomiting. Moreover, it remains unclear whether the gastrointestinal symptoms are caused by direct infection of the gastrointestinal tract by SARS-CoV-2 or are the result of systemic immune activation and subsequent dysregulation of homeostatic mechanisms. This review provides a brief overview of the mechanisms by which SARS-CoV-2 disrupts the integrity of the gastrointestinal barrier including the mechanical barrier, chemical barrier, microbial barrier, and immune barrier.
10.3748/wjg.v29.i15.2283
Contributions of the intestinal microbiome in lung immunity.
McAleer Jeremy P,Kolls Jay K
European journal of immunology
The intestine is a critical site of immune cell development that not only controls intestinal immunity but extra-intestinal immunity as well. Recent findings have highlighted important roles for gut microbiota in shaping lung inflammation. Here, we discuss interactions between the microbiota and immune system including T cells, protective effects of microbiota on lung infections, the role of diet in shaping the composition of gut microbiota and susceptibility to asthma, epidemiologic evidence implicating antibiotic use and microbiota in asthma and clinical trials investigating probiotics as potential treatments for atopy and asthma. The systemic effects of gut microbiota are partially attributed to their generating metabolites including short chain fatty acids, which can suppress lung inflammation through the activation of G protein-coupled receptors. Thus, studying the interactions between microbiota and immune cells can lead to the identification of therapeutic targets for chronic lower respiratory diseases.
10.1002/eji.201646721
Role of the microbiome in swine respiratory disease.
Niederwerder Megan C
Veterinary microbiology
Microbiome is a term used to describe the community of microorganisms that live on the skin and mucosal surfaces of animals. The gastrointestinal microbiome is essential for proper nutrition and immunity. How the gastrointestinal microbiome impacts primary respiratory or systemic infections is an emerging area of study. Porcine reproductive and respiratory syndrome (PRRS) is caused by a systemic virus infection with primary lung pathology and continues to be the most costly disease of swine worldwide. Recent studies have demonstrated that improved outcome after experimental infection with PRRS virus and porcine circovirus type 2 (PCV2) is associated with increased fecal microbiome diversity and the presence of non-pathogenic Escherichia coli. In this review, we will discuss the factors that influence microbiome development in swine, associations of the microbiome with growth and immunity during infection with respiratory pathogens, and the role of the microbiome in PRRS. Taken together, modulation of the microbiome may be an alternative tool in the control of PRRS due to its intricate role in digestion of nutrients, systemic immunity, and response to pulmonary infections.
10.1016/j.vetmic.2017.02.017
Gut-Lung Axis: Microbial Crosstalk in Pediatric Respiratory Tract Infections.
Zhu Wenxia,Wu Yilin,Liu Hui,Jiang Caini,Huo Lili
Frontiers in immunology
The gut microbiota is an important regulator for maintaining the organ microenvironment through effects on the gut-vital organs axis. Respiratory tract infections are one of the most widespread and harmful diseases, especially in the last 2 years. Many lines of evidence indicate that the gut microbiota and its metabolites can be considered in therapeutic strategies to effectively prevent and treat respiratory diseases. However, due to the different gut microbiota composition in children compared to adults and the dynamic development of the immature immune system, studies on the interaction between children's intestinal flora and respiratory infections are still lacking. Here, we describe the changes in the gut microbiota of children with respiratory tract infections and explain the relationship between the microbiota of children with their immune function and disease development. In addition, we will provide perspectives on the direct manipulation of intestinal microbes to prevent or treat pediatric respiratory infections.
10.3389/fimmu.2021.741233
Probiotics in Treatment of Viral Respiratory Infections and Neuroinflammatory Disorders.
Shahbazi Roghayeh,Yasavoli-Sharahi Hamed,Alsadi Nawal,Ismail Nafissa,Matar Chantal
Molecules (Basel, Switzerland)
Inflammation is a biological response to the activation of the immune system by various infectious or non-infectious agents, which may lead to tissue damage and various diseases. Gut commensal bacteria maintain a symbiotic relationship with the host and display a critical function in the homeostasis of the host immune system. Disturbance to the gut microbiota leads to immune dysfunction both locally and at distant sites, which causes inflammatory conditions not only in the intestine but also in the other organs such as lungs and brain, and may induce a disease state. Probiotics are well known to reinforce immunity and counteract inflammation by restoring symbiosis within the gut microbiota. As a result, probiotics protect against various diseases, including respiratory infections and neuroinflammatory disorders. A growing body of research supports the beneficial role of probiotics in lung and mental health through modulating the gut-lung and gut-brain axes. In the current paper, we discuss the potential role of probiotics in the treatment of viral respiratory infections, including the COVID-19 disease, as major public health crisis in 2020, and influenza virus infection, as well as treatment of neurological disorders like multiple sclerosis and other mental illnesses.
10.3390/molecules25214891
Microbiota as a potentially-modifiable factor influencing COVID-19.
Current opinion in virology
Impacts of respiratory tract viruses have long been appreciated to highly heterogeneous both between and within various populations. The SARS-CoV-2 pandemic, which is the first time that a pathogen's spread across the globe has been extensively monitored by direct detection of the pathogen itself rather just than the morbidity left in its wake, indicates such heterogeneity is not limited to outcomes of infections but whether infection of a particular host occurs at all. This suggests an important role for yet to be discovered environmental (i.e. non-genetic) factors that influence whether an exposure to the virus initiates a productive infection and, moreover, the severity of disease that results. This article discusses the emerging hypothesis that the composition of a host's commensal microbial communities, that is, its 'microbiome', may be one such determinant that influences outcomes following encounters with respiratory viral pathogens in general and SARS-CoV-2 in particular. Specifically, we will review the rationales and evidence that supports this hypothesis and, moreover, speculate as to possible approaches to manipulate microbiota to ameliorate disease induced by respiratory viral pathogens.
10.1016/j.coviro.2021.04.005
Lung Microbiota and Its Impact on the Mucosal Immune Phenotype.
Wu Benjamin G,Segal Leopoldo N
Microbiology spectrum
The use of culture-independent techniques has allowed us to appreciate that the upper and lower respiratory tract contain a diverse community of microbes in health and disease. Research has only recently explored the effects of the microbiome on the host immune response. The exposure of the human body to the bacterial environment is an important factor for immunological development; thus, the interaction between the microbiome and its host is critical to understanding the pathogenesis of disease. In this article, we discuss the mechanisms that determine the composition of the airway microbiome and its effects on the host immune response. With the use of ecological principles, we have learned how the lower airways constitute a unique niche subjected to frequent microbial migration (e.g., through aspiration) and constant immunological pressure. The discussion will focus on the possible inflammatory pathways that are up- and downregulated when the immune system is challenged by dysbiosis. Identification of potential markers and microbial targets to address the modulation of inflammation in early disease, when changes may have the most effect, will be critical for future therapies.
10.1128/microbiolspec.BAD-0005-2016
The Role of the Microbiome in the Developmental Origins of Health and Disease.
Pediatrics
Although the prominent role of the microbiome in human health has been established, the early-life microbiome is now being recognized as a major influence on long-term human health and development. Variations in the composition and functional potential of the early-life microbiome are the result of lifestyle factors, such as mode of birth, breastfeeding, diet, and antibiotic usage. In addition, variations in the composition of the early-life microbiome have been associated with specific disease outcomes, such as asthma, obesity, and neurodevelopmental disorders. This points toward this bacterial consortium as a mediator between early lifestyle factors and health and disease. In addition, variations in the microbial intrauterine environment may predispose neonates to specific health outcomes later in life. A role of the microbiome in the Developmental Origins of Health and Disease is supported in this collective research. Highlighting the early-life critical window of susceptibility associated with microbiome development, we discuss infant microbial colonization, beginning with the maternal-to-fetal exchange of microbes in utero and up through the influence of breastfeeding in the first year of life. In addition, we review the available disease-specific evidence pointing toward the microbiome as a mechanistic mediator in the Developmental Origins of Health and Disease.
10.1542/peds.2017-2437
Severe acute respiratory syndrome coronavirus-2 infection and the gut-liver axis.
Mohandas Sundhar,Vairappan Balasubramaniyan
Journal of digestive diseases
Patients affected by coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, manifest various gastrointestinal and hepatic abnormalities alongside respiratory disorders. The identification of this virus in the feces of more than 50% of infected individuals indicates the possibility of viral shedding and fecal-to-oral transmission. Preliminary reports have also identified alterations in the intestinal microbiota profile in infected individuals. Moreover, COVID-19 patients manifest various degrees of liver injury characterized by alterations in liver enzymes. Digestive symptoms and liver abnormalities correlate with disease severity, the incidence of critical outcomes and patient's recovery. However, the pathogenic mechanisms behind COVID-19-induced abnormalities in the gut-liver axis seem to be multifactorial in origin. This review compiles current knowledge sourced from preclinical and clinical research and summarizes gastrointestinal and hepatic dysfunctions observed following SARS-CoV-2 infection, and also explores the possible mechanisms generating abnormalities in the gut-liver axis. Furthermore, this review sheds light on possible therapeutic targets against these disorders.
10.1111/1751-2980.12951
Revitalizing myocarditis treatment through gut microbiota modulation: unveiling a promising therapeutic avenue.
Frontiers in cellular and infection microbiology
Numerous studies have demonstrated that gut microbiota plays an important role in the development and treatment of different cardiovascular diseases, including hypertension, heart failure, myocardial infarction, arrhythmia, and atherosclerosis. Furthermore, evidence from recent studies has shown that gut microbiota contributes to the development of myocarditis. Myocarditis is an inflammatory disease that often results in myocardial damage. Myocarditis is a common cause of sudden cardiac death in young adults. The incidence of myocarditis and its associated dilated cardiomyopathy has been increasing yearly. Myocarditis has gained significant attention on social media due to its association with both COVID-19 and COVID-19 vaccinations. However, the current therapeutic options for myocarditis are limited. In addition, little is known about the potential therapeutic targets of myocarditis. In this study, we review (1) the evidence on the gut-heart axis, (2) the crosslink between gut microbiota and the immune system, (3) the association between myocarditis and the immune system, (4) the impact of gut microbiota and its metabolites on myocarditis, (5) current strategies for modulating gut microbiota, (6) challenges and future directions for targeted gut microbiota in the treatment of myocarditis. The approach of targeting the gut microbiota in myocarditis is still in its infancy, and this is the study to explore the gut microbiota-immune system-myocarditis axis. Our findings are expected to pave the way for the use of gut microbiota as a potential therapeutic target in the treatment of myocarditis.
10.3389/fcimb.2023.1191936
Distal Consequences of Mucosal Infections in Intestinal and Lung Inflammation.
Frontiers in immunology
Infectious diseases are one of the leading causes of morbidity and mortality worldwide, affecting high-risk populations such as children and the elderly. Pathogens usually activate local immune responses at the site of infection, resulting in both protective and inflammatory responses, which may lead to local changes in the microbiota, metabolites, and the cytokine environment. Although some pathogens can disseminate and cause systemic disease, increasing evidence suggests that local infections can affect tissues not directly invaded. In particular, diseases occurring at distal mucosal barriers such as the lung and the intestine seem to be linked, as shown by epidemiological studies in humans. These mucosal barriers have bidirectional interactions based mainly on multiple signals derived from the microbiota, which has been termed as the gut-lung axis. However, the effects observed in such distal places are still incompletely understood. Most of the current research focuses on the systemic impact of changes in microbiota and bacterial metabolites during infection, which could further modulate immune responses at distal tissue sites. Here, we describe how the gut microbiota and associated metabolites play key roles in maintaining local homeostasis and preventing enteric infection by direct and indirect mechanisms. Subsequently, we discuss recent murine and human studies linking infectious diseases with changes occurring at distal mucosal barriers, with particular emphasis on bacterial and viral infections affecting the lung and the gastrointestinal tract. Further, we discuss the potential mechanisms by which pathogens may cause such effects, promoting either protection or susceptibility to secondary infection.
10.3389/fimmu.2022.877533
Can SARS-CoV-2 be transmitted via faeces?
Current opinion in gastroenterology
PURPOSE OF REVIEW:COVID-19 patients can present gastrointestinal symptoms, being diarrhoea one of the most frequent, suggesting intestinal health can be impacted by COVID-19. Here, we will discuss whether there is a correlation between the presence of SARS-CoV-2 RNA in faeces and diarrhoea, the relevance of gastrointestinal symptoms in disease diagnosis and transmission, and how COVID-19 can impact the gut microbial balance. RECENT FINDINGS:SARS-CoV-2 RNA has been reported in faeces or rectal swabs of COVID-19 patients with and without diarrhoea, suggesting faecal shedding can occur independently of gastrointestinal symptoms. However, the presence of the virus in the intestine can persist beyond its presence in the respiratory tract, with some reports suggesting that SARS-CoV-2 in the faeces can be infectious.COVID-19 can impact the gut microbiota causing an enhancement of biosynthesis pathways that favour the expansion of bacterial pathogens in the inflamed gut, and causing a decline in commensals involved in the human immune response. SUMMARY:Gastrointestinal symptoms may be the first indication of COVID-19. SARS-CoV-2 in faeces can potentiate routes of disease transmission, particularly as the high viral loads reported in patients with severe illness suggest virus replication in the intestine may be possible.
10.1097/MOG.0000000000000794
Role of the Microbiota in Lung Cancer: Insights on Prevention and Treatment.
International journal of molecular sciences
The microbiota is increasingly recognized as a critical player in cancer onset and progression and response to cancer chemotherapy treatment. In recent years, several preclinical and clinical studies have evidenced the involvement of microbiota in lung cancer, one of the world's deadliest cancers. However, the mechanisms by which the microbiota can impact this type of cancer and patient survival and response to treatments remain poorly investigated. In this review, the peculiarities of the gut and lung microbial ecosystems have been highlighted, and recent findings illustrating the possible mechanisms underlying the microbiota-lung cancer interaction and the host immune response have been discussed. In addition, the mucosal immune system has been identified as a crucial communication frame to ease interactive dynamics between the immune system and the microbiota. Finally, the use of specific next-generation intestinal probiotic strains in counteracting airway diseases has been evaluated. We believe that restoring homeostasis and the balance of bacterial microflora should become part of the routine of integrated cancer interventions, using probiotics, prebiotics, and postbiotics, and promoting a healthy diet and lifestyle.
10.3390/ijms23116138
Roles of the gut microbiota in severe SARS-CoV-2 infection.
Cytokine & growth factor reviews
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. The pathophysiological mechanisms linking gut dysbiosis and severe SARS-CoV-2 infection are poorly understood, although gut microbiota disorders are related to severe SARS-CoV-2 infections. The roles of the gut microbiota in severe SARS-CoV-2 infection were compared with those in respiratory viral infection, which is an easily understood and enlightening analogy. Secondary bacterial infections caused by immune disorders and antibiotic abuse can lead to dysregulation of the gut microbiota in patients with respiratory viral infections. The gut microbiota can influence the progression of respiratory viral infections through metabolites and the immune response, which is known as the gut-lung axis. Angiotensin-converting enzyme 2 is expressed in both the lungs and the small intestine, which may be a bridge between the lung and the gut. Similarly, SARS-CoV-2 infection has been shown to disturb the gut microbiota, which may be the cause of cytokine storms. Bacteria in the gut, lung, and other tissues and respiratory viruses can be considered microecosystems and may exert overall effects on the host. By referencing respiratory viral infections, this review focused on the mechanisms involved in the interaction between SARS-CoV-2 infections and the gut microbiota and provides new strategies for the treatment or prevention of severe SARS-CoV-2 infections by improving gut microbial homeostasis.
10.1016/j.cytogfr.2022.01.007
The Role of Angiotensin Converting Enzyme 2 in Modulating Gut Microbiota, Intestinal Inflammation, and Coronavirus Infection.
Penninger Josef M,Grant Maria B,Sung Joseph J Y
Gastroenterology
The role of angiotensin converting enzyme 2 has expanded from regulating the renin angiotensin system to regulating intestinal amino acid homeostasis and the gut microbiome. Recently, angiotensin converting enzyme 2 was identified as a primary receptor for severe acute respiratory syndrome coronaviruses 1 and 2 being expressed in multiple tissues including the luminal surface of the gut. In this brief perspective, we examine the role of angiotensin converting enzyme 2 as the receptor for severe acute respiratory syndrome coronavirus 2 and the impact of coronavirus disease 19 infection on the gut microbiome and on the gut epithelium.
10.1053/j.gastro.2020.07.067
The infant gut bacterial microbiota and risk of pediatric asthma and allergic diseases.
Johnson Christine C,Ownby Dennis R
Translational research : the journal of laboratory and clinical medicine
Among the many areas being revolutionized by the recent introduction of culture-independent microbial identification techniques is investigation of the relationship between close contact with large animals, antibiotics, breast feeding, mode of birth, and other exposures during infancy as related to a reduced risk of asthma and allergic disease. These exposures were originally clustered under the "Hygiene Hypothesis" which has evolved into the "Microbiota Hypothesis". This review begins by summarizing epidemiologic studies suggesting that the common feature of these allergy risk-related exposures is their influence on the founding and early development of a child's gut microbiota. Next, studies using culture-independent techniques are presented showing that children who have experienced the exposures of interest have altered gut microbiota. Finally, selected mouse and human studies are presented which begin to corroborate the protective exposures identified in epidemiologic studies by elucidating mechanisms through which microbes can alter immune development and function. These microbially driven immune alterations demonstrate that microbial exposures in many cases could alter the risk of subsequent allergic disease and asthma. Hopefully, a better understanding of how microbes influence allergic disease will lead to safe and effective methods for reducing the prevalence of all forms of allergic disease.
10.1016/j.trsl.2016.06.010
Probiotics as a biotherapeutics for the management and prevention of respiratory tract diseases.
Microbiology and immunology
Respiratory diseases are responsible for a greater mortality rate around the world. Viral or bacterial infections in the respiratory tract have been identified as major causative agents for death and disability among the population. Respiratory tract infections (RTIs) cause severe respiratory ailments starting from coldlike symptoms, eventually affecting the lungs and other viscera, and are mainly categorized into two types depending on the affected area: upper RTIs and lower RTIs. Respiratory viruses belong to several viral families such as influenza virus, enterovirus, adenovirus, respiratory syncytial virus, and recently severe acute respiratory syndrome coronavirus 2. Studies have indicated that people with good immune functions are less prone to respiratory infections and also their recovery rate is quicker. Innate and acquired immune systems actively participate in the recognition and elimination of the pathogenic agents. In the present context, the potential of probiotics is recognized as viable microorganisms that support the balance of the beneficial microbial population in the gastrointestinal tract and promote host immunity. The probiotics have long been known to regulate bodily immune functions and have been used against general RTIs such as cough, pharyngitis, laryngitis, pneumonia, and asthma. In addition, intervention with probiotics could directly affect the composition of the gut microbiota that have been shown to palliate respiratory diseases by modulating pulmonary immune activities through the gut-lung axis, and therefore, probiotics could become an alternative therapeutic approach for RTIs.
10.1111/1348-0421.12980
The microbiome of the lung.
Translational research : the journal of laboratory and clinical medicine
Investigation of the lung microbiome is a relatively new field. Although the lungs were classically believed to be sterile, recently published investigations have identified microbial communities in the lungs of healthy humans. At the present time, there are significant methodologic and technical hurdles that must be addressed in ongoing investigations, including distinguishing the microbiota of the upper and lower respiratory tracts. However, characterization of the lung microbiome is likely to provide important pathogenic insights into cystic fibrosis, respiratory disease of the newborn, chronic obstructive pulmonary disease, and asthma. In addition to characterization of the lung microbiome, the microbiota of the gastrointestinal tract have profound influence on the development and maintenance of lung immunity and inflammation. Further study of gastrointestinal-respiratory interactions is likely to yield important insights into the pathogenesis of pulmonary diseases, including asthma. As this field advances over the next several years, we anticipate that studies using larger cohorts, multicenter designs, and longitudinal sampling will add to our knowledge and understanding of the lung microbiome.
10.1016/j.trsl.2012.02.005
Host responses to mucosal biofilms in the lung and gut.
Mucosal immunology
The impact of the human microbiome on health and disease is of utmost importance and has been studied intensively in recent years. Microbes promote immune system development and are essential to the production and absorption of nutrients for the host but are also implicated in disease pathogenesis. Particularly, bacterial biofilms have long been recognized as contributors to chronic infections and diseases in humans. However, our understanding of how the host responds to the presence of biofilms, specifically the immune response to biofilms, and how this contributes to disease pathogenesis is limited. This review aims to highlight what is known about biofilm formation and in vivo models available for the biofilm study. We critique the contribution of biofilms to human diseases, focusing on the lung diseases, cystic fibrosis and chronic obstructive pulmonary disease, and the gut diseases, inflammatory bowel disease and colorectal cancer.
10.1038/s41385-020-0270-1
The role of atopy in asthma development and persistence.
Di Cicco Maria,D'Elios Sofia,Peroni Diego G,Comberiati Pasquale
Current opinion in allergy and clinical immunology
PURPOSE OF REVIEW:Asthma is the most common chronic disease in pediatric age. Childhood-onset asthma, as opposed to adult-onset asthma, is typically characterized by a personal and often a family history of atopy and related markers of type 2-mediated inflammation. However, the interplay between atopy and asthma development is more complex than a linear dose-response relationship. RECENT FINDINGS:Family and personal history of atopic diseases have been confirmed as major risk factors for asthma occurrence and persistence in children. Early life and multiple sensitizations to aeroallergens significantly increase the risk of asthma development in school age. Early life lower respiratory tract viral infections, especially caused by rhinovirus, also increase the susceptibility to atopic asthma in childhood. Human rhinovirus type C receptor CDHR3 polymorphisms have been shown to affect receptor epithelial expression, activation, and asthma development and exacerbation severity in children. Atopic sensitization and respiratory viral infections can synergistically enhance the susceptibility to asthma through multiple mechanisms, including the IgE-mediated inhibition of innate antiviral responses to rhinovirus. Emerging evidence shows that several nonatopic factors are also involved in the asthma pathogenesis in genetically predisposed individuals, including early life exposure to environmental factors, and lung and gut microbiome composition. SUMMARY:The current review outlines recent data on the complex role of atopy in asthma pathogenesis and persistence, and addresses new research topics such as the role of epigenetics and the lung microbiome.
10.1097/ACI.0000000000000627
The clinical implications of the microbiome in the development of allergy diseases.
Koidl Larissa,Untersmayr Eva
Expert review of clinical immunology
: A substantial number of patients worldwide are affected by allergies. Emerging evidence suggests that the individual microbial composition might contribute to the development of allergies or might even protect from allergic diseases.: This review provides a detailed summary regarding available knowledge on the composition of a healthy human microbiome at allergy relevant body sites. It highlights factors influencing the microbiota composition. Furthermore, recent findings on the mutual interaction of the microbiota with the innate and adaptive immune system are reported. In the final part, this knowledge is combined to discuss microbial implications for food allergy, allergic asthma, allergic rhinitis, and skin allergies. Literature for this review was gathered by searching PubMed and Google Scholar databases between October and December 2020.: Due to the highly individual composition, it is currently not possible to define the characteristics of a site-specific microbiome in health and disease. Mainly effects of bacterial communities have been investigated, while fungal or viral influences are not yet well understood. The communication between microbial communities found in different organs impact on allergy development. Thus, a personalized approach is essential to beneficially influence these complex interactions and to modulate the host-specific microbiota in allergies.
10.1080/1744666X.2021.1874353
Host microbiome-pathogen interactions in pediatric infections.
Current opinion in infectious diseases
PURPOSE OF REVIEW:In this review, we discuss recent research that has furthered our understanding of microbiome development during childhood, the role of the microbiome in infections during this life stage, and emerging opportunities for microbiome-based therapies for infection prevention or treatment in children. RECENT FINDINGS:The microbiome is highly dynamic during childhood and shaped by a variety of host and environmental factors. In turn, the microbiome influences risk and severity of a broad range of infections during childhood, with recent studies highlighting potential roles in respiratory, gastrointestinal, and systemic infections. The microbiome exerts this influence through both direct interactions with potential pathogens and indirectly through modulation of host immune responses. The elucidation of some of these mechanisms by recent studies and the development of effective microbiome-based therapies for adults with recurrent Clostridioides difficile infection highlight the enormous promise that targeting the microbiome has for reducing the burden of infectious diseases during childhood. SUMMARY:The microbiome has emerged as a key modifier of infection susceptibility and severity among children. Further research is needed to define the roles of microbes other than bacteria and to elucidate the mechanisms underlying microbiome-host and microbiome-pathogen interactions of importance to infectious diseases in children.
10.1097/QCO.0000000000000949
Asthma and obesity: endotoxin another insult to add to injury?
Clinical science (London, England : 1979)
Low-grade inflammation is often an underlying cause of several chronic diseases such as asthma, obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). Defining the mediators of such chronic low-grade inflammation often appears dependent on which disease is being investigated. However, downstream systemic inflammatory cytokine responses in these diseases often overlap, noting there is no doubt more than one factor at play to heighten the inflammatory response. Furthermore, it is increasingly believed that diet and an altered gut microbiota may play an important role in the pathology of such diverse diseases. More specifically, the inflammatory mediator endotoxin, which is a complex lipopolysaccharide (LPS) derived from the outer membrane cell wall of Gram-negative bacteria and is abundant within the gut microbiota, and may play a direct role alongside inhaled allergens in eliciting an inflammatory response in asthma. Endotoxin has immunogenic effects and is sufficiently microscopic to traverse the gut mucosa and enter the systemic circulation to act as a mediator of chronic low-grade inflammation in disease. Whilst the role of endotoxin has been considered in conditions of obesity, cardiovascular disease and T2DM, endotoxin as an inflammatory trigger in asthma is less well understood. This review has sought to examine the current evidence for the role of endotoxin in asthma, and whether the gut microbiota could be a dietary target to improve disease management. This may expand our understanding of endotoxin as a mediator of further low-grade inflammatory diseases, and how endotoxin may represent yet another insult to add to injury.
10.1042/CS20210790
Early gut microbiota intervention in premature infants: Application perspectives.
Journal of advanced research
BACKGROUND:Preterm birth is the leading cause of death in children under the age of five. One of the major factors contributing to the high risk of diseases and deaths in premature infants is the incomplete development of the intestinal immune system. The gut microbiota has been widely recognized as a critical factor in promoting the development and function of the intestinal immune system after birth. However, the gut microbiota of premature infants is at high risk of dysbiosis, which is highly associated with adverse effects on the development and education of the early life immune system. Early intervention can modulate the colonization and development of gut microbiota and has a long-term influence on the development of the intestinal immune system. AIM OF REVIEW:This review aims to summarize the characterization, interconnection, and underlying mechanism of gut microbiota and intestinal innate immunity in premature infants, and to discuss the status, applicability, safety, and prospects of different intervention strategies in premature infants, thus providing an overview and outlook of the current applications and remaining gaps of early intervention strategies in premature infants. KEY SCIENTIFIC CONCEPTS OF REVIEW:This review is focused on three key concepts. Firstly, the gut microbiota of premature infants is at high risk of dysbiosis, resulting in dysfunctional intestinal immune system processes. Secondly, contributing roles of early intervention have been observed in improving the intestinal environment and promoting gut microbiota colonization, which is significant in the development and function of gut immunity in premature infants. Thirdly, different strategies of early intervention, such as probiotics, fecal microbiota transplantation, and nutrients, show different safety, applicability, and outcome in premature infants, and the underlying mechanism is complex and poorly understood.
10.1016/j.jare.2022.11.004
The gut microbiome: Relationships with disease and opportunities for therapy.
The Journal of experimental medicine
Over the past decade, our view of human-associated microbes has expanded beyond that of a few species toward an appreciation of the diverse and niche-specialized microbial communities that develop in the human host with chronological age. The largest reservoir of microbes exists in the distal gastrointestinal tract, both in the lumen, where microbes facilitate primary and secondary metabolism, and on mucosal surfaces, where they interact with host immune cell populations. While local microbial-driven immunomodulation in the gut is well described, more recent studies have demonstrated a role for the gut microbiome in influencing remote organs and mucosal and hematopoietic immune function. Unsurprisingly, therefore, perturbation to the composition and function of the gut microbiota has been associated with chronic diseases ranging from gastrointestinal inflammatory and metabolic conditions to neurological, cardiovascular, and respiratory illnesses. Considerable effort is currently focused on understanding the natural history of microbiome development in humans in the context of health outcomes, in parallel with improving our knowledge of microbiome-host molecular interactions. These efforts ultimately aim to develop effective approaches to rehabilitate perturbed human microbial ecosystems as a means to restore health or prevent disease. This review details the role of the gut microbiome in modulating host health with a focus on immunomodulation and discusses strategies for manipulating the gut microbiome for the management or prevention of chronic inflammatory conditions.
10.1084/jem.20180448
Therapeutic immunoglobulin A antibody for dysbiosis-related diseases.
International immunology
Dysbiosis is alterations in the microbial composition compared with a healthy microbiota and often features a reduction in gut microbial diversity and a change in microbial taxa. Dysbiosis, especially in the gut, has also been proposed to play a crucial role in the pathogenesis of a wide variety of diseases, including inflammatory bowel disease, colorectal cancer, cardiovascular disease, obesity, diabetes and multiple sclerosis. A body of evidence has shown that intestinal polymeric immunoglobulin A (IgA) antibodies are important to regulate the gut microbiota as well as to exclude pathogenic bacteria or viral infection such as influenza and SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) at mucosal sites. Since the 1970s, trials for oral administration of therapeutic IgA or IgG have been performed mainly to treat infectious enteritis caused by pathogenic Escherichia coli or Clostridium difficile. However, few of them have been successfully developed for clinical application up to now. In addition to the protective function against intestinal pathogens, IgA is well known to modulate the gut commensal microbiota leading to symbiosis. Nevertheless, the development of therapeutic IgA drugs to treat dysbiosis is not progressing. In this review, the advantages of therapeutic IgA antibodies and the problems for their development will be discussed.
10.1093/intimm/dxab066
Potential intestinal infection and faecal-oral transmission of SARS-CoV-2.
Nature reviews. Gastroenterology & hepatology
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to more than 200 countries and regions globally. SARS-CoV-2 is thought to spread mainly through respiratory droplets and close contact. However, reports have shown that a notable proportion of patients with coronavirus disease 2019 (COVID-19) develop gastrointestinal symptoms and nearly half of patients confirmed to have COVID-19 have shown detectable SARS-CoV-2 RNA in their faecal samples. Moreover, SARS-CoV-2 infection reportedly alters intestinal microbiota, which correlated with the expression of inflammatory factors. Furthermore, multiple in vitro and in vivo animal studies have provided direct evidence of intestinal infection by SARS-CoV-2. These lines of evidence highlight the nature of SARS-CoV-2 gastrointestinal infection and its potential faecal-oral transmission. Here, we summarize the current findings on the gastrointestinal manifestations of COVID-19 and its possible mechanisms. We also discuss how SARS-CoV-2 gastrointestinal infection might occur and the current evidence and future studies needed to establish the occurrence of faecal-oral transmission.
10.1038/s41575-021-00416-6
The pediatric microbiome and the lung.
Current opinion in pediatrics
PURPOSE OF REVIEW:Many pediatric lung diseases are characterized by infection. These infections are generally diagnosed, studied, and treated using standard culture methods to identify 'traditional pathogens'. Based on these techniques, healthy lungs have generally been thought to be sterile. However, recent advances in culture-independent microbiological techniques challenged this paradigm by identifying diverse microbes in respiratory specimens (respiratory microbiomes) from both healthy people and those with diverse lung diseases. In addition, growing evidence suggests a link between gastrointestinal microbiomes and inflammatory diseases of various mucosal surfaces, including airways. RECENT FINDINGS:This article reviews the rapidly developing field of respiratory microbiome research, emphasizing recent progress made employing increasingly sophisticated technologies. Although many of the relevant studies have focused on adults with cystic fibrosis, recent research has included children and adults with other respiratory diseases, as well as healthy individuals. These studies suggest that even healthy children have airway microbiomes, and that both respiratory and gastrointestinal microbiomes often differ between healthy people and those with different types and severities of airway disease. The causal relationships between microbiomes, disease type and progression, and treatments such as antibiotics must now be defined. SUMMARY:The advent of culture-independent microbiological techniques has transformed how we think about the relationship between microbes and airway disease. More research is required to translate these findings to improved therapies and preventive strategies.
10.1097/MOP.0000000000000212
Nutrients and Microbiota in Lung Diseases of Prematurity: The Placenta-Gut-Lung Triangle.
Nutrients
Cardiorespiratory function is not only the foremost determinant of life after premature birth, but also a major factor of long-term outcomes. However, the path from placental disconnection to nutritional autonomy is enduring and challenging for the preterm infant and, at each step, will have profound influences on respiratory physiology and disease. Fluid and energy intake, specific nutrients such as amino-acids, lipids and vitamins, and their ways of administration -parenteral or enteral-have direct implications on lung tissue composition and cellular functions, thus affect lung development and homeostasis and contributing to acute and chronic respiratory disorders. In addition, metabolomic signatures have recently emerged as biomarkers of bronchopulmonary dysplasia and other neonatal diseases, suggesting a profound implication of specific metabolites such as amino-acids, acylcarnitine and fatty acids in lung injury and repair, inflammation and immune modulation. Recent advances have highlighted the profound influence of the microbiome on many short- and long-term outcomes in the preterm infant. Lung and intestinal microbiomes are deeply intricated, and nutrition plays a prominent role in their establishment and regulation. There is an emerging evidence that human milk prevents bronchopulmonary dysplasia in premature infants, potentially through microbiome composition and/or inflammation modulation. Restoring antibiotic therapy-mediated microbiome disruption is another potentially beneficial action of human milk, which can be in part emulated by pre- and probiotics and supplements. This review will explore the many facets of the gut-lung axis and its pathophysiology in acute and chronic respiratory disorders of the prematurely born infant, and explore established and innovative nutritional approaches for prevention and treatment.
10.3390/nu12020469
COVID-19 and Gut Injury.
Nutrients
COVID-19 induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a pandemic and it has led to more than 620 million patients with 6.56 million deaths globally. Males are more susceptible to COVID-19 infection and associated with a higher chance to develop severe COVID-19 than females. Aged people are at a high risk of COVID-19 infection, while young children have also increased cases. COVID-19 patients typically develop respiratory system pathologies, however symptoms in the gastrointestinal (GI) tract are also very common. Inflammatory cell recruitments and their secreted cytokines are found in the GI tract in COVID-19 patients. Microbiota changes are the key feature in COVID-19 patients with gut injury. Here, we review all current known mechanisms of COVID-19-induced gut injury, and the most acceptable one is that SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) receptor on host cells in the GI tract. Interestingly, inflammatory bowel disease (IBD) is an inflammatory disorder, but the patients with IBD do not have the increased risk to develop COVID-19. There is currently no cure for COVID-19, but anti-viruses and monoclonal antibodies reduce viral load and shorten the recovery time of the disease. We summarize current therapeutics that target symptoms in the GI tract, including probiotics, ACE2 inhibitors and nutrients. These are promising therapeutic options for COVID-19-induced gut injury.
10.3390/nu14204409
The Intersection of Parkinson's Disease, Viral Infections, and COVID-19.
Rosen Benjamin,Kurtishi Alberim,Vazquez-Jimenez Gonzalo R,Møller Simon Geir
Molecular neurobiology
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of human COVID-19, not only causes flu-like symptoms and gut microbiome complications but a large number of infected individuals also experience a host of neurological symptoms including loss of smell and taste, seizures, difficulty concentrating, decreased alertness, and brain inflammation. Although SARS-CoV-2 infections are not more prevalent in Parkinson's disease patients, a higher mortality rate has been reported not only associated with older age and longer disease duration, but also through several mechanisms, such as interactions with the brain dopaminergic system and through systemic inflammatory responses. Indeed, a number of the neurological symptoms seen in COVID-19 patients, as well as the alterations in the gut microbiome, are also prevalent in patients with Parkinson's disease. Furthermore, biochemical pathways such as oxidative stress, inflammation, and protein aggregation have shared commonalities between Parkinson's disease and COVID-19 disease progression. In this review, we describe and compare the numerous similarities and intersections between neurodegeneration in Parkinson's disease and RNA viral infections, emphasizing the current SARS-CoV-2 global health crisis.
10.1007/s12035-021-02408-8
Microbiota-Dependent Regulation of Antimicrobial Immunity in the Lung.
Maschirow Laura,Suttorp Norbert,Opitz Bastian
American journal of respiratory cell and molecular biology
Several body sites, including the intestinal and respiratory tracts, are colonized with a myriad of bacteria, archaea, fungi, and viruses, which are collectively referred to as the "microbiota." The bacterial component of the microbiota in particular has been recognized to influence a multitude of physiological functions, including innate and adaptive immune responses. Germ-free and microbiota-depleted animals display an impaired antimicrobial defense and are therefore highly susceptible to various infections, including those affecting the lung. In this review, we summarize current understanding of how the microbiota affects antimicrobial immunity and disease tolerance during viral and bacterial pulmonary infections. A better understanding of these mechanisms could help to refine clinical approaches to preserve or rescue the microbiota-immune system interplay and protect patients against lung infections.
10.1165/rcmb.2019-0101TR
Inborn errors of immunity and related microbiome.
Frontiers in immunology
Inborn errors of immunity (IEI) are characterized by diverse clinical manifestations that are dominated by atypical, recurrent, chronic, or severe infectious or non-infectious features, including autoimmunity, lymphoproliferative disease, granulomas, and/or malignancy, which contribute substantially to morbidity and mortality. Some data suggest a correlation between clinical manifestations of IEI and altered gut microbiota. Many IEI display microbial dysbiosis resulting from the proliferation of pro-inflammatory bacteria or a decrease in anti-inflammatory bacteria with variations in the composition and function of numerous microbiota. Dysbiosis is considered more established, mainly within common variable immunodeficiency, selective immunoglobulin A deficiency, severe combined immunodeficiency diseases, Wiskott-Aldrich syndrome, Hyper-IgE syndrome, autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED), immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome, IL-10 receptor deficiency, chronic granulomatous disease, and Kostmann disease. For certain IEIs, the specific predominance of gastrointestinal, respiratory, and cutaneous involvement, which is frequently associated with dysbiosis, justifies the interest for microbiome identification. With the better understanding of the relationship between gut microbiota, host immunity, and infectious diseases, the integration of microbiota modulation as a therapeutic approach or a preventive measure of infection becomes increasingly relevant. Thus, a promising strategy is to develop optimized prebiotics, probiotics, postbiotics, and fecal microbial transplantation to rebalance the intestinal microbiota and thereby attenuate the disease activity of many IEIs.
10.3389/fimmu.2022.982772
Role of microbiota on lung homeostasis and diseases.
Wang Jian,Li Fengqi,Tian Zhigang
Science China. Life sciences
The lungs, as a place of gas exchange, are continuously exposed to environmental stimuli, such as allergens, microbes, and pollutants. The development of the culture-independent technique for microbiological analysis, such as 16S rRNA sequencing, has uncovered that the lungs are not sterile and, in fact, colonized by diverse communities of microbiota. The function of intestinal microbiota in modulating mucosal homeostasis and defense has been widely studied; however, the potential function of lung microbiota in regulating immunity and homeostasis has just begun. Increasing evidence indicates the relevance of microbiota to lung homeostasis and disease. In this review, we describe the distribution and composition of microbiota in the respiratory system and discuss the potential function of lung microbiota in both health and acute/chronic lung disease. In addition, we also discuss the recent understanding of the gut-lung axis, because several studies have revealed that the immunological interaction among the gut, the lung, and the microbiota was involved in this issue.
10.1007/s11427-017-9151-1
Gut microecological regulation on bronchiolitis and asthma in children: A review.
The clinical respiratory journal
INTRODUCTION:Asthma and bronchiolitis in children are considered common clinical problems associated with gut microbiota. However, the exact relationship between gut microbiota and the above-mentioned diseases remains unclear. Here, we discussed recent advances in understanding the potential mechanism underlying immune regulation of gut microbiota on asthma and bronchiolitis in children as well as the role of the gut-lung axis. METHODS:We retrieved and assessed all relevant original articles related to gut microbiota, airway inflammation-induced wheezing in children, and gut-lung axis studies from databases that have been published so far, including PubMed/MEDLINE, Scopus, Google Scholar, China National Knowledge Infrastructure (CNKI) and the Wanfang Database. RESULTS:The infant period is critical for the development of gut microbiota, which can be influenced by gestational age, delivery mode, antibiotic exposure and feeding mode. The gut microbiota in children with asthma and bronchiolitis is significantly distinct from those in healthy subjects. Gut microbiota dysbiosis is implicated in asthma and bronchiolitis in children. The presence of intestinal disturbances in lung diseases highlights the importance of the gut-lung axis. CONCLUSION:Gut microbiota dysbiosis potentially increases the risk of asthma and bronchiolitis in children. Moreover, a deeper understanding of the gut-lung axis with regard to the gut microbiota of children with respiratory diseases could contribute to clinical practice for pulmonary diseases.
10.1111/crj.13622
Herbal medicine in the treatment of COVID-19 based on the gut-lung axis.
Acupuncture and herbal medicine
Respiratory symptoms are most commonly experienced by patients in the early stages of novel coronavirus disease 2019 (COVID-19). However, with a better understanding of COVID-19, gastrointestinal symptoms such as diarrhea, nausea, and vomiting have attracted increasing attention. The gastrointestinal tract may be a target organ of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The intestinal microecological balance is a crucial factor for homeostasis, including immunity and inflammation, which are closely related to COVID-19. Herbal medicine can restore intestinal function and regulate the gut flora structure. Herbal medicine has a long history of treating lung diseases from the perspective of the intestine, which is called the gut-lung axis. The physiological activities of guts and lungs influence each other through intestinal flora, microflora metabolites, and mucosal immunity. Microecological modulators are included in the diagnosis and treatment protocols for COVID-19. In this review, we demonstrate the relationship between COVID-19 and the gut, gut-lung axis, and the role of herbal medicine in treating respiratory diseases originating from the intestinal tract. It is expected that the significance of herbal medicine in treating respiratory diseases from the perspective of the intestinal tract could lead to new ideas and methods for treatment. Graphical abstract:http://links.lww.com/AHM/A33.
10.1097/HM9.0000000000000038
Gut Microbiome Alterations in COVID-19.
Genomics, proteomics & bioinformatics
Since the outset of the coronavirus disease 2019 (COVID-19) pandemic, the gut microbiome in COVID-19 has garnered substantial interest, given its significant roles in human health and pathophysiology. Accumulating evidence is unveiling that the gut microbiome is broadly altered in COVID-19, including the bacterial microbiome, mycobiome, and virome. Overall, the gut microbial ecological network is significantly weakened and becomes sparse in patients with COVID-19, together with a decrease in gut microbiome diversity. Beyond the existence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the gut microbiome of patients with COVID-19 is also characterized by enrichment of opportunistic bacteria, fungi, and eukaryotic viruses, which are also associated with disease severity and presentation. Meanwhile, a multitude of symbiotic bacteria and bacteriophages are decreased in abundance in patients with COVID-19. Such gut microbiome features persist in a significant subset of patients with COVID-19 even after disease resolution, coinciding with 'long COVID' (also known as post-acute sequelae of COVID-19). The broadly-altered gut microbiome is largely a consequence of SARS-CoV-2infection and its downstream detrimental effects on the systemic host immunity and the gut milieu. The impaired host immunity and distorted gut microbial ecology, particularly loss of low-abundance beneficial bacteria and blooms of opportunistic fungi including Candida, may hinder the reassembly of the gut microbiome post COVID-19. Future investigation is necessary to fully understand the role of the gut microbiome in host immunity against SARS-CoV-2 infection, as well as the long-term effect of COVID-19 on the gut microbiome in relation to the host health after the pandemic.
10.1016/j.gpb.2021.09.004
Role of Micronutrients and Gut Microbiota-Derived Metabolites in COVID-19 Recovery.
International journal of molecular sciences
A balanced and varied diet provides diverse beneficial effects on health, such as adequate micronutrient availability and a gut microbiome in homeostasis. Besides their participation in biochemical processes as cofactors and coenzymes, vitamins and minerals have an immunoregulatory function; meanwhile, gut microbiota and its metabolites coordinate directly and indirectly the cell response through the interaction with the host receptors. Malnourishment is a crucial risk factor for several pathologies, and its involvement during the Coronavirus Disease 2019 pandemic has been reported. This pandemic has caused a significant decline in the worldwide population, especially those with chronic diseases, reduced physical activity, and elder age. Diet and gut microbiota composition are probable causes for this susceptibility, and its supplementation can play a role in reestablishing microbial homeostasis and improving immunity response against Coronavirus Disease 2019 infection and recovery. This study reviews the role of micronutrients and microbiomes in the risk of infection, the severity of disease, and the Coronavirus Disease 2019 sequelae.
10.3390/ijms232012324
Targeting the Pulmonary Microbiota to Fight against Respiratory Diseases.
Cells
The mucosal immune system of the respiratory tract possesses an effective "defense barrier" against the invading pathogenic microorganisms; therefore, the lungs of healthy organisms are considered to be sterile for a long time according to the strong pathogens-eliminating ability. The emergence of next-generation sequencing technology has accelerated the studies about the microbial communities and immune regulating functions of lung microbiota during the past two decades. The acquisition and maturation of respiratory microbiota during childhood are mainly determined by the birth mode, diet structure, environmental exposure and antibiotic usage. However, the formation and development of lung microbiota in early life might affect the occurrence of respiratory diseases throughout the whole life cycle. The interplay and crosstalk between the gut and lung can be realized by the direct exchange of microbial species through the lymph circulation, moreover, the bioactive metabolites produced by the gut microbiota and lung microbiota can be changed via blood circulation. Complicated interactions among the lung microbiota, the respiratory viruses, and the host immune system can regulate the immune homeostasis and affect the inflammatory response in the lung. Probiotics, prebiotics, functional foods and fecal microbiota transplantation can all be used to maintain the microbial homeostasis of intestinal microbiota and lung microbiota. Therefore, various kinds of interventions on manipulating the symbiotic microbiota might be explored as novel effective strategies to prevent and control respiratory diseases.
10.3390/cells11050916
Microbiota-Gut-Brain Communication in the SARS-CoV-2 Infection.
Cells
The coronavirus disease of 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome 2 (SARS-CoV-2). In addition to pneumonia, individuals affected by the disease have neurological symptoms. Indeed, SARS-CoV-2 has a neuroinvasive capacity. It is known that the infection caused by SARS-CoV-2 leads to a cytokine storm. An exacerbated inflammatory state can lead to the blood-brain barrier (BBB) damage as well as to intestinal dysbiosis. These changes, in turn, are associated with microglial activation and reactivity of astrocytes that can promote the degeneration of neurons and be associated with the development of psychiatric disorders and neurodegenerative diseases. Studies also have been shown that SARS-CoV-2 alters the composition and functional activity of the gut microbiota. The microbiota-gut-brain axis provides a bidirectional homeostatic communication pathway. Thus, this review focuses on studies that show the relationship between inflammation and the gut microbiota-brain axis in SARS-CoV-2 infection.
10.3390/cells10081993
Role of microbiome in the pathophysiology and disease course of asthma.
Singanayagam Aran,Ritchie Andrew I,Johnston Sebastian L
Current opinion in pulmonary medicine
PURPOSE OF REVIEW:The emergence of next-generation 16S rRNA sequencing techniques has facilitated a more detailed study of the body's microbiota and led to renewed interest in the association between microbial exposure and asthma inception. In this review, we evaluate the evidence that the respiratory tract and intestinal microbiota contribute to asthma pathogenesis and progression. RECENT FINDINGS:Human studies have revealed associations between the presence of potentially pathogenic bacteria in the respiratory tract in early life and subsequent risk of allergic sensitization and asthma. Similarly, alterations in the intestinal microbiota of neonates have also been shown to precede the development of asthma. Emerging evidence suggests that the lung microbiota is dysregulated in asthma with specific changes in bacterial diversity and community composition according to severity and phenotype. Studies using germ-free mice have been invaluable in moving our understanding from correlation to causation by demonstrating a mechanistic link between the neonatal microbiota and the development of allergic airway inflammation. SUMMARY:An expanding body of literature supports the hypothesis that early life microbial exposures and bacterial communities within the lung and/or intestine play an important role in shaping early immunological development. Perturbations in the microbiota may promote immune defects associated with the development of asthma and allergic sensitization.
10.1097/MCP.0000000000000333
Microbiome Anomalies in Allogeneic Hematopoietic Cell Transplantation.
Annual review of medicine
The microbiome is an integrated part of the human body that can modulate a variety of disease processes and affect prognosis, treatment response, complications, and outcomes. The importance of allogeneic hematopoietic cell transplantation in cancer treatment has resulted in extensive investigations on the interaction between the microbiome and this treatment modality. These investigations are beginning to lead to clinical trials of microbiome-targeted interventions. Here we review some of these discoveries and describe strategies being investigated to manipulate the microbiome for favorable outcomes, such as the proper selection and timing of antibiotics, type of diet and route of administration, probiotics, prebiotics, and fecal microbiota transplantation.
10.1146/annurev-med-052918-122440
The microbiome and development of allergic disease.
Lynch Susan V,Boushey Homer A
Current opinion in allergy and clinical immunology
PURPOSE OF REVIEW:First, to review how the global rise in prevalence of asthma prompted studies of the relationships between microbial exposure in early infancy, the rate and pattern of development of immune function, and the development of allergic sensitization and of wheezing in childhood. And, second, to review how those studies laid the groundwork for a possible strategy for primary prevention of asthma through manipulation of the microbiome of the gastrointestinal and/or respiratory tracts. RECENT FINDINGS:Atopy and asthma are complex diseases thought to result from a 'gene-by-environment' interaction; the rapidity of their rise in prevalence points to a change in environment as most likely causal. Epidemiologic studies noting associations between events in infancy and later development of atopic diseases have suggested that their rise in prevalence is related to a deficiency in microbial exposure in early life. The findings from birth cohort studies of humans and from interventional studies of mice converge in suggesting that a deficiency in microbial colonization of the respiratory or gastrointestinal tract by certain commensal microbes results in skewed development of systemic and/or local immune function that increases susceptibility to allergic sensitization and to viral lower respiratory infection. Recent studies are now honing in on identifying the microbes, or collection of microbes, whose collective functions are necessary for induction of immune tolerance, and thus of reduced susceptibility. SUMMARY:Atopy and asthma appear to have their roots in an insufficiency of early-life exposure to the diverse environmental microbiota necessary to ensure colonization of the gastrointestinal and/or respiratory tracts with the commensal microbes necessary for induction of balanced, toleragenic immune function. Identification of the commensal bacteria necessary, now ever closer at hand, will lay the groundwork for the development of strategies for primary prevention of atopic disease, especially of childhood asthma.
10.1097/ACI.0000000000000255
The Role of the Microbiome in Asthma: The Gut⁻Lung Axis.
Frati Franco,Salvatori Cristina,Incorvaia Cristoforo,Bellucci Alessandro,Di Cara Giuseppe,Marcucci Francesco,Esposito Susanna
International journal of molecular sciences
Asthma is one of the most common chronic respiratory diseases worldwide. It affects all ages but frequently begins in childhood. Initiation and exacerbations may depend on individual susceptibility, viral infections, allergen exposure, tobacco smoke exposure, and outdoor air pollution. The aim of this review was to analyze the role of the gut⁻lung axis in asthma development, considering all asthma phenotypes, and to evaluate whether microbe-based therapies may be used for asthma prevention. Several studies have confirmed the role of microbiota in the regulation of immune function and the development of atopy and asthma. These clinical conditions have apparent roots in an insufficiency of early life exposure to the diverse environmental microbiota necessary to ensure colonization of the gastrointestinal and/or respiratory tracts. Commensal microbes are necessary for the induction of a balanced, tolerogenic immune system. The identification of commensal bacteria in both the gastroenteric and respiratory tracts could be an innovative and important issue. In conclusion, the function of microbiota in healthy immune response is generally acknowledged, and gut dysbacteriosis might result in chronic inflammatory respiratory disorders, particularly asthma. Further investigations are needed to improve our understanding of the role of the microbiome in inflammation and its influence on important risk factors for asthma, including tobacco smoke and host genetic features.
10.3390/ijms20010123
Cross-talk between immune system and microbiota in COVID-19.
Expert review of gastroenterology & hepatology
INTRODUCTION:Human gut microbiota plays a crucial role in providing protective responses against pathogens, particularly by regulating immune system homeostasis. There is a reciprocal interaction between the gut and lung microbiota, called the gut-lung axis (GLA). Any alteration in the gut microbiota or their metabolites can cause immune dysregulation, which can impair the antiviral activity of the immune system against respiratory viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. AREAS COVERED:This narrative review mainly outlines emerging data on the mechanisms underlying the interactions between the immune system and intestinal microbial dysbiosis, which is caused by an imbalance in the levels of essential metabolites. The authors will also discuss the role of probiotics in restoring the balance of the gut microbiota and modulation of cytokine storm. EXPERT OPINION:Microbiota-derived signals regulate the immune system and protect different tissues during severe viral respiratory infections. The GLA's equilibration could help manage the mortality and morbidity rates associated with SARS-CoV-2 infection.
10.1080/17474124.2021.1991311
Diet, Probiotics and Their Impact on the Gut Microbiota during the COVID-19 Pandemic.
Nutrients
SARS-CoV-2 infection is associated with diverse clinical manifestations, immune dysfunction, and gut microbiota alterations. The nutritional and biochemical quality of one's diet can influence the intestinal microbiota, which may play a role in the defense mechanisms against potential pathogens, by promoting a wide variety of immune-host interactions. In the COVID-19 pandemic, besides the development of pharmacological therapies, a healthy balanced diet, rich with food-derived antioxidants, may be a useful strategy. Many studies demonstrated that vitamins and probiotic therapies have positive effects on the treatment and prevention of oxidative stress and inflammation in COVID-19. The ecology of the gut microbiota in the digestive tract has been linked to the transport function of the host receptor known as angiotensin converting enzyme 2 (ACE2), suggesting that COVID-19 may be related to the gut microbiota. The angiotensin converting enzyme (ACE), and its receptor (ACE2), play central roles in modulating the renin-angiotensin system (RAS). In addition, ACE2 has functions that act independently of the RAS. ACE2 is the receptor for the SARS coronavirus, and ACE2 is essential for the expression of neutral amino acid transporters in the gut. In this context, ACE2 modulates innate immunity and influences the composition of the gut microbiota. Malnutrition is one of the leading underlying causes of morbidity and mortality worldwide and, including comorbidities, may be a major cause of worse outcomes and higher mortality among COVID-19 patients. This paper reviews the research on dietary components, with particular emphasis on vitamins, antioxidants, and probiotic therapies, and their impacts on the intestinal microbiota's diversity during the SARS-CoV-2 pandemic.
10.3390/nu13093172
Topical Microbial Therapeutics against Respiratory Viral Infections.
Spacova Irina,De Boeck Ilke,Bron Peter A,Delputte Peter,Lebeer Sarah
Trends in molecular medicine
Emerging evidence suggests that microbial therapeutics can prevent and treat respiratory viral diseases, especially when applied directly to the airways. This review presents established beneficial effects of locally administered microbial therapeutics against respiratory viral diseases and the inferred related molecular mechanisms. Several mechanisms established in the intestinal probiotics field as well as novel, niche-specific insights are relevant in the airways. Studies at cellular and organism levels highlight biologically plausible but strain-specific and host and virus context-dependent mechanisms, underlying the potential of beneficial bacteria. Large-scale clinical studies can now be rationally designed to provide a bench-to-bedside translation of the multifactorial bacterial mechanisms within the host respiratory tract, to diminish the incidence and severity of viral infections and the concomitant complications.
10.1016/j.molmed.2021.03.009
Early-immune development in asthma: A review of the literature.
Cellular immunology
This review presents a comprehensive examination of the various factors contributing to the immunopathogenesis of asthma from the prenatal to preschool period. We focus on the contributions of genetic and environmental components as well as the role of the nasal and gut microbiome on immune development. Predisposing genetic factors, including inherited genes associated with increased susceptibility to asthma, are discussed alongside environmental factors such as respiratory viruses and pollutant exposure, which can trigger or exacerbate asthma symptoms. Furthermore, the intricate interplay between the nasal and gut microbiome and the immune system is explored, emphasizing their influence on allergic immune development and response to environmental stimuli. This body of literature underscores the necessity of a comprehensive approach to comprehend and manage asthma, as it emphasizes the interactions of multiple factors in immune development and disease progression.
10.1016/j.cellimm.2023.104770
The origins of allergy from a systems approach.
Krempski James Walter,Dant Christopher,Nadeau Kari C
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology
OBJECTIVE:The origins of allergic diseases have traditionally been explained by immunoglobulin E-mediated immune responses to account for asthma, atopic dermatitis, atopic rhinitis, and food allergy. Research insights into disease origins support a broader array of factors that predispose, initiate, or exacerbate altered immunity in allergic diseases, such as (1) inherent epithelial barrier dysfunction; (2) loss of immune tolerance; (3) disturbances in the gut; and (4) organ-specific microbiomes, diet, and age. Here, we discuss these influences that together form a better understanding of allergy as a systems disease. DATA SOURCES:We summarize recent advances in epithelial dysfunction, environmental influences, inflammation, infection, alterations in the specific microbiome, and inherent genetic predisposition. STUDY SELECTIONS:We performed a literature search targeting primary and review articles. RESULTS:We explored microbial-epithelial-immune interactions underlying the early-life origins of allergic disorders and evaluated immune mechanisms suggesting novel disease prevention or intervention strategies. Damage to epithelial surfaces lies at the origin of various manifestations of allergic disease. As a sensor of environmental stimuli, the epithelium of the lungs, gut, and skin is affected by an altered microbiome, air pollution, food allergens in a changed diet, and chemicals in modern detergents. This collectively leads to alterations of lung, skin, or gut epithelial surfaces, driving a type 2 immune response that underlies atopic diseases. Treatment and prevention of allergic diseases include biologics, oral desensitization, targeted gut microbiome alterations, and changes in behavior. CONCLUSION:Understanding the spectrum of allergy as a systems disease will allow us to better define the mechanisms of allergic disorders and improve their treatment.
10.1016/j.anai.2020.07.013
Gut Microbiota Dysbiosis as a Target for Improved Post-Surgical Outcomes and Improved Patient Care: A Review of Current Literature.
Mustansir Dawoodbhoy Fatema,Patel Bharati Kadamb,Patel Kadamb,Bhatia Madhav,Lee Chuen Neng,Moochhala Shabbir M
Shock (Augusta, Ga.)
ABSTRACT:Critical illness results in significant changes in the human gut microbiota, leading to the breakdown of the intestinal barrier function, which plays a role in the pathogenesis of multiple organ dysfunction. Patients with sepsis/acute respiratory distress syndrome (ARDS) have a profoundly distorted intestinal microbiota rhythm, which plays a considerable role in the development of gut-derived infections and intestinal dysbiosis. Despite recent medical developments, postsurgical complications are associated with a high morbidity and mortality rate. Bacterial translocation, which is the movement of bacteria and bacterial products across the intestinal barrier, was shown to be a mechanism behind sepsis. Current research is focusing on a solution by addressing significant factors that contribute to intestinal dysbiosis, which subsequently leads to multiple organ failure and, thus, mortality. It may, however, be challenging to manipulate the microbiota in critically ill patients for enhanced therapeutic gain. Probiotic manipulation is advantageous for maintaining the gut-barrier defense and for modulating the immune response. Based on available published research, this review aims to address the application of potential strategies in the intensive care unit, supplemented with current therapeutics by the administration of probiotics, prebiotics, and fecal microbiota transplant, to reduce post-surgical complications of sepsis/ARDS in critically ill patients.
10.1097/SHK.0000000000001654
The role of gut microbiota in atopic asthma and allergy, implications in the understanding of disease pathogenesis.
Salameh Mohammad,Burney Zain,Mhaimeed Nada,Laswi Ibrahim,Yousri Noha A,Bendriss Ghizlane,Zakaria Dalia
Scandinavian journal of immunology
Asthma is a clinical syndrome characterized by chronic airway inflammation. There is mounting evidence on the role of microbiota in the development of asthma. This review focuses on the role of microbiota in maintaining the integrity of the epithelia and their role in regulating the immune response. The review compiles data from multiple studies on the role of microbiota in the innate immune response and the development and differentiation of CD4 T cells, a major component of the adaptive arm of the immune response. As a result of dysbiosis, invariant natural killer T cells may induce T helper 2 cell differentiation and immunoglobulin E isotype switching through the release of interleukin-4 and interleukin-13. Furthermore, degradation of immunoglobulin A antibodies, increased circulating mast cells and basophils, and inflammation are among other mechanisms by which dysbiosis can induce or exacerbate asthma. After explaining the underlying mechanisms, the review derives conclusions from studies that investigate dysbiosis in infancy and the development of asthma later in life. The review also includes studies that investigate asthmatic mothers and the development of asthma in children and the role of dysbiosis in that regard. Finally, the review explains the statistical relationship between eczema and asthma through multiple studies that investigate the role of dysbiosis in both atopic states. This review provides insight into the role of dysbiosis in asthma, and an understanding that is required to establish clinical trials which aim to modulate the gut microbiota as a means of preventing and treating asthma.
10.1111/sji.12855
Biomarkers in idiopathic pulmonary fibrosis.
Drakopanagiotakis F,Wujak Lukasz,Wygrecka Malgorzata,Markart P
Matrix biology : journal of the International Society for Matrix Biology
Idiopathic pulmonary fibrosis (IPF) is a chronic, debilitating, fibrotic lung disease leading to respiratory failure and ultimately to death. Being the prototype of interstitial lung diseases, IPF is characterized by marked heterogeneity regarding its clinical course. Despite significant progress in the understanding of its pathogenesis, we still cannot reliably predict the course of the disease and the response to treatment of an individual patient. Non-invasive biomarkers, in particular serum biomarkers, for the (early) diagnosis, differential diagnosis, prognosis and prediction of therapeutic response are urgently needed. Numerous molecules involved in alveolar epithelial cell injury, fibroproliferation and matrix remodeling as well as immune regulation have been proposed as potential biomarkers. Furthermore, genetic variants of TOLLIP, MUC5B, and other genes are associated with a differential response to treatment and with the development and/or the prognosis of IPF. Additionally, the bacterial signature in IPF lungs, as shown from microbiome analyses, as well as mitochondrial DNA seem to have promising roles as biomarkers. Moreover, combination of multiple biomarkers may identify comprehensive biomarker signatures in IPF patients. However, there is still a long way until these potential biomarkers complete or substitute for the clinical and functional parameters currently available for IPF.
10.1016/j.matbio.2018.01.023
Microbiome as a Target for Cancer Therapy.
Suraya Ratoe,Nagano Tatsuya,Kobayashi Kazuyuki,Nishimura Yoshihiro
Integrative cancer therapies
Recently, the microbiome has been gaining traction as a major player regulating various functions that correlate with many pathological conditions, including cancer. The central gut microbiota population has the capability to regulate normal inflammatory, immune, and metabolic functions, and disturbance in the balance of the normal microbiota population can subsequently induce pathological responses that closely relate with the mechanistic development and progression of cancer in various forms and sites. As a disease with major socioeconomic burden partly due to its current therapeutic options, modulating the imbalanced gut microbiota represents a novel option not only as an adjuvant therapy to relieve cancer treatment-related symptoms but also to influence cancer progression itself. In this review, we will discuss how the microbiome, specifically the gut microbiota, could affect cancer pathogenesis and what the effect of gut microbiota-targeting treatment options have on the many aspects of cancer pathologies based on the knowledge of recent years.
10.1177/1534735420920721
Gastrointestinal microbiota: A predictor of COVID-19 severity?
World journal of gastroenterology
Coronavirus disease 2019 (COVID-19), caused by a severe acute respiratory syndrome coronavirus 2 infection, has raised serious concerns worldwide over the past 3 years. The severity and clinical course of COVID-19 depends on many factors ( associated comorbidities, age, ) and may have various clinical and imaging findings, which raises management concerns. Gut microbiota composition is known to influence respiratory disease, and respiratory viral infection can also influence gut microbiota. Gut and lung microbiota and their relationship (gut-lung axis) can act as modulators of inflammation. Modulating the intestinal microbiota, by improving its composition and diversity through nutraceutical agents, can have a positive impact in the prophylaxis/treatment of COVID-19.
10.3748/wjg.v28.i45.6328
The Human Microbiome in the Fight Against Tuberculosis.
Wood Madeleine R,Yu Elaine A,Mehta Saurabh
The American journal of tropical medicine and hygiene
AbstractThe human microbiome is an intriguing potentially modifiable risk factor in our arsenal against , the leading infectious disease killer globally. Previous studies have shown associations between the human microbiome and pulmonary disease states; however, etiological links between the microbiome and tuberculosis (TB) infection or disease remain unclear. Immunomodulatory roles of the microbiome may prove to be a critical asset in the host response against TB, including in preventing TB infection, reducing progression from latency, mitigating disease severity, and lowering the incidence of drug resistance and coinfections. This review examined the associations between TB and the gut and lung microbiome. Eight studies were identified through a PubMed database search, including one animal study ( = 1), case report ( = 1), and case-control studies ( = 6). TB infection and disease were associated with reduced gastrointestinal microbial diversity in a murine model and human case report. Sputum microbial diversity differed by TB status in case-control studies, although some reported heterogeneous findings. Current evidence suggests that the gut and lung microbiome are associated with TB infection and disease. However, as studies are limited, etiological and longitudinal research is needed to determine clinical relevance.
10.4269/ajtmh.16-0581
Commensal Fungi in Health and Disease.
Limon Jose J,Skalski Joseph H,Underhill David M
Cell host & microbe
Fungi are increasingly being recognized as common members of the microbiomes found on nearly all mucosal surfaces, and interest is growing in understanding how these organisms may contribute to health and disease. In this review, we investigate recent developments in our understanding of the fungal microbiota or "mycobiota" including challenges faced in characterizing it, where these organisms are found, their diversity, and how they interact with host immunity. Growing evidence indicates that, like the bacterial microbiota, the fungal microbiota is often altered in disease states, and increasingly studies are being designed to probe the functional consequences of such fungal dysbiosis on health and disease.
10.1016/j.chom.2017.07.002
The relationship between gut microbiota and COVID-19 progression: new insights into immunopathogenesis and treatment.
Frontiers in immunology
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a global health crisis. Increasing evidence underlines the key role of competent immune responses in resisting SARS-CoV-2 infection and manifests the disastrous consequence of host immune dysregulation. Elucidating the mechanisms responsible for deregulated host immunity in COVID-19 may provide a theoretical basis for further research on new treatment modalities. Gut microbiota comprises trillions of microorganisms colonizing the human gastrointestinal tract and has a vital role in immune homeostasis and the gut-lung crosstalk. Particularly, SARS-CoV-2 infection can lead to the disruption of gut microbiota equilibrium, a condition called gut dysbiosis. Due to its regulatory effect on host immunity, gut microbiota has recently received considerable attention in the field of SARS-CoV-2 immunopathology. Imbalanced gut microbiota can fuel COVID-19 progression through production of bioactive metabolites, intestinal metabolism, enhancement of the cytokine storm, exaggeration of inflammation, regulation of adaptive immunity and other aspects. In this review, we provide an overview of the alterations in gut microbiota in COVID-19 patients, and their effects on individuals' susceptibility to viral infection and COVID-19 progression. Moreover, we summarize currently available data on the critical role of the bidirectional regulation between intestinal microbes and host immunity in SARS-CoV-2-induced pathology, and highlight the immunomodulatory mechanisms of gut microbiota contributing to COVID-19 pathogenesis. In addition, we discuss the therapeutic benefits and future perspectives of microbiota-targeted interventions including faecal microbiota transplantation (FMT), bacteriotherapy and traditional Chinese medicine (TCM) in COVID-19 treatment.
10.3389/fimmu.2023.1180336
External exposome and allergic respiratory and skin diseases.
Cecchi Lorenzo,D'Amato Gennaro,Annesi-Maesano Isabella
The Journal of allergy and clinical immunology
Allergies are complex diseases that result from interactions between multiple genetic and environmental factors. However, the increase in allergies observed in the past decades is explained exclusively by environmental changes occurring in the same period. Presently, the exposome, the totality of specific and nonspecific external environmental exposures (external exposome) to which a subject is exposed from preconception onward and their consequences at the organ and cell levels (internal exposome), is being considered to explain the inception, development, and exacerbations of allergic diseases. Among the best-studied environmental factors of the specific external exposome, indoor and outdoor aeroallergens and air pollutants play a key role in the etiopathogenesis of the inflammatory response to allergens and in clinical manifestations of allergic disease. Climate change, urbanization, and loss of biodiversity affect sources, emissions, and concentrations of main aeroallergens and air pollutants and are among the most critical challenges facing the health and quality of life of the still increasing number of allergic patients today and in the coming decades. Thunderstorm-related asthma is a dramatic example of the effects of combined environmental factors and an in vivo model for understanding the mechanisms at work in respiratory allergy. Environment- or lifestyle-driven aberrancies in the gut and skin microbiome composition represent key mediators of allergic diseases. A better knowledge of the effect of the external exposome on allergy development is crucial for urging patients, health professionals, and policymakers to take actions to mitigate the effect of environmental changes and to adapt to them.
10.1016/j.jaci.2018.01.016
Human Gut Microbiota in Health and Selected Cancers.
International journal of molecular sciences
The majority of the epithelial surfaces of our body, and the digestive tract, respiratory and urogenital systems, are colonized by a vast number of bacteria, archaea, fungi, protozoans, and viruses. These , particularly those of the intestines, play an important, beneficial role in digestion, metabolism, and the synthesis of vitamins. Their metabolites stimulate cytokine production by the human host, which are used against potential pathogens. The composition of the microbiota is influenced by several internal and external factors, including diet, age, disease, and lifestyle. Such changes, called dysbiosis, may be involved in the development of various conditions, such as metabolic diseases, including metabolic syndrome, type 2 diabetes mellitus, Hashimoto's thyroidis and Graves' disease; they can also play a role in nervous system disturbances, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, and depression. An association has also been found between gut microbiota dysbiosis and cancer. Our health is closely associated with the state of our microbiota, and their homeostasis. The aim of this review is to describe the associations between human gut microbiota and cancer, and examine the potential role of gut microbiota in anticancer therapy.
10.3390/ijms222413440
Effects of Intestinal Fungi and Viruses on Immune Responses and Inflammatory Bowel Diseases.
Iliev Iliyan D,Cadwell Ken
Gastroenterology
The intestinal microbiota comprises diverse fungal and viral components, in addition to bacteria. These microbes interact with the immune system and affect human physiology. Advances in metagenomics have associated inflammatory and autoimmune diseases with alterations in fungal and viral species in the gut. Studies of animal models have found that commensal fungi and viruses can activate host-protective immune pathways related to epithelial barrier integrity, but can also induce reactions that contribute to events associated with inflammatory bowel disease. Changes in our environment associated with modernization and the COVID-19 pandemic have exposed humans to new fungi and viruses, with unknown consequences. We review the lessons learned from studies of animal viruses and fungi commonly detected in the human gut and how these might affect health and intestinal disease.
10.1053/j.gastro.2020.06.100
Impact of COVID-19 on the Intestinal Microbiome.
Venegas-Borsellino Carla,Sankararaman Senthilkumar,Roche Keelin,Burns JBracken,Landis Ryan Michael
Current nutrition reports
PURPOSE OF REVIEW:This review article aims to explore the GI changes induced by SARS-CoV-2 and how gut microbial homeostasis can influence these changes and affect the lung-gut axis and its relationship with the induction of the cytokine release syndrome in severe COVID-19 patients. RECENT FINDINGS:Coronavirus disease 2019 (COVID-19) affects not only the respiratory system but can produce multi-systemic damage. The expression of angiotensin-converting enzyme 2 (ACE-2) receptors in the gastrointestinal (GI) tract, the high prevalence of GI symptoms in severely ill COVID-19 patients, and the abnormalities described in the gut microbiome in these patients have raised concerns about the influence of GI tract as a risk factor or as a potential modulator to reduce the severity of COVID-19. Understanding the mechanisms by which gut dysbiosis may influence viral transmission and disease progression in COVID-19 may help in shaping how accessible therapies, like diet modulation, can potentially help beat the devastating consequences of COVID-19.
10.1007/s13668-021-00375-z
Crosstalk Between the Gut Microbiota and Epithelial Cells Under Physiological and Infectious Conditions.
Zhou An,Yuan Yi,Yang Min,Huang Yujiao,Li Xin,Li Shengpeng,Yang Shiming,Tang Bo
Frontiers in cellular and infection microbiology
The gastrointestinal tract (GIT) is considered the largest immunological organ, with a diverse gut microbiota, that contributes to combatting pathogens and maintaining human health. Under physiological conditions, the crosstalk between gut microbiota and intestinal epithelial cells (IECs) plays a crucial role in GIT homeostasis. Gut microbiota and derived metabolites can compromise gut barrier integrity by activating some signaling pathways in IECs. Conversely, IECs can separate the gut microbiota from the host immune cells to avoid an excessive immune response and regulate the composition of the gut microbiota by providing an alternative energy source and releasing some molecules, such as hormones and mucus. Infections by various pathogens, such as bacteria, viruses, and parasites, can disturb the diversity of the gut microbiota and influence the structure and metabolism of IECs. However, the interaction between gut microbiota and IECs during infection is still not clear. In this review, we will focus on the existing evidence to elucidate the crosstalk between gut microbiota and IECs during infection and discuss some potential therapeutic methods, including probiotics, fecal microbiota transplantation (FMT), and dietary fiber. Understanding the role of crosstalk during infection may help us to establish novel strategies for prevention and treatment in patients with infectious diseases, such as infection, HIV, and COVID-19.
10.3389/fcimb.2022.832672
Fecal Microbiota Transplantation during and Post-COVID-19 Pandemic.
International journal of molecular sciences
COVID-19 is a major pandemic facing the world today, which has implications on current microbiome-based treatments such as fecal microbiota transplantation (FMT) used for recurrent infections. The bidirectional relationship between the inhabitants of our gut, the gut microbiota, and COVID-19 pathogenesis, as well as the underlying mechanism involved, must be elucidated in order to increase FMT safety and efficacy. In this perspective, we discuss the crucial cross-talk between the gut microbiota and the lungs, known as the gut-lung axis, during COVID-19 infection, as well as the putative effect of these microorganisms and their functional activity (i.e., short chain fatty acids and bile acids) on FMT treatment. In addition, we highlight the urgent need to investigate the possible impact of COVID-19 on FMT safety and efficacy, as well as instilling stringent screening protocols of donors and recipients during COVID-19 and post-COVID-19 pandemic to produce a cohesive and optimized FMT treatment plan across all centers and in all countries across the globe.
10.3390/ijms22063004
Attaching clinical significance to COVID-19-associated diarrhea.
Life sciences
The Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), erupted in 2020 and created severe public health and socioeconomic challenges worldwide. A subset of patients, in addition to presenting with typical features such as fever, cough and dyspnea, was also afflicted with diarrhea. However, the clinical features and prognoses related to COVID-19-associated diarrhea have not attracted sufficient attention. This review of the medical literature examines the incidence, pathogenesis, clinical characteristics, fecal virus changes, prognoses and influencing factors of COVID-19-associated diarrhea. The reported incidence of diarrhea in patients with COVID-19 ranged from 2% to 49.5%. The main cause of diarrhea was found to be invasive by SARS-CoV-2 of ACE-2-expressing epithelial cells of the small intestine, causing local intestinal damage. This cellular invasion may be the key factor for the much longer duration of SARS-CoV-2 positivity observed for feces compared to pharyngeal swabs. The associated diarrhea in these patients upsets the balance of intestinal flora, resulting in more-severe disease intensity and worse prognosis. Clinicians should be vigilant to this kind of COVID-19-associated diarrhea, and design more effective prevention and treatment options for patients with positive fecal nucleic acid tests and intestinal microflora disorders.
10.1016/j.lfs.2020.118312
A comprehensive perspective on the interaction between gut microbiota and COVID-19 vaccines.
Gut microbes
The efficacy of COVID-19 vaccines varies between individuals and populations, and the reasons for this are still not fully understood. Recent clinical studies and animal models have indicated that the gut microbiota may influence the immunogenicity of the vaccine and, thus, its effectiveness. This suggests that there is a bidirectional relationship between the gut microbiota and the COVID-19 vaccine, with the varying components of the microbiota either enhancing or reducing the vaccine's efficacy. To put an end to the spread of the COVID-19 pandemic, the necessity of vaccines that create powerful and long-term immunity is now more important than ever, and understanding the role of the gut microbiota in this process is essential. Conversely, COVID-19 vaccines also have a significant effect on the gut microbiota, decreasing its total number of organisms and the variety of species present. In this Review, we analyze the evidence that suggesting an interaction between the gut microbiota and COVID-19 vaccine effectiveness, consider the immunological mechanisms that may be responsible for this connection, and explore the possibility of using gut microbiota-focused interventions to improve the efficacy of COVID-19 vaccines.
10.1080/19490976.2023.2233146
The microbiota-mediated dietary and nutritional interventions for COVID-19.
Clinical immunology (Orlando, Fla.)
Worldwide, scientists are looking for specific treatment for COVID-19. Apart from the antiviral approach, the interventions to support healthy immune responses to the virus are feasible through diet, nutrition, and lifestyle approaches. This narrative review explores the recent studies on dietary, nutritional, and lifestyle interventions that influence the microbiota-mediated immunomodulatory effects against viral infections. Cumulative studies reported that the airway microbiota and SARS-CoV-2 leverage each other and determine the pathogen-microbiota-host responses. Cigarette smoking can disrupt microbiota abundance. The composition and diversification of intestinal microbiota influence the airway microbiota and the innate and adaptive immunity, which require supports from the balance of macro- and micronutrients from the diet. Colorful vegetables supplied fermentable prebiotics and anti-inflammatory, antioxidant phytonutrients. Fermented foods and beverages support intestinal microbiota. In sensitive individuals, the avoidance of the high immunoreactive food antigens contributes to antiviral immunity. This review suggests associations between airway and intestinal microbiota, antiviral host immunity, and the influences of dietary, nutritional, and lifestyle interventions to prevent the clinical course toward severe COVID-19.
10.1016/j.clim.2021.108725
From Pre- and Probiotics to Post-Biotics: A Narrative Review.
International journal of environmental research and public health
BACKGROUND AND AIMS:gut microbiota (GM) is a complex ecosystem containing bacteria, viruses, fungi, and yeasts. It has several functions in the human body ranging from immunomodulation to metabolic. GM derangement is called dysbiosis and is involved in several host diseases. Pre-, probiotics, and symbiotics (PRE-PRO-SYMB) have been extensively developed and studied for GM re-modulation. Herein, we review the literature data regarding the new concept of postbiotics, starting from PRE-PRO-SYMB. METHODS:we conducted a search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials, and case series using the following keywords and acronyms and their associations: gut microbiota, prebiotics, probiotics, symbiotic, and postbiotics. RESULTS:postbiotics account for PRO components and metabolic products able to beneficially affect host health and GM. The deeper the knowledge about them, the greater their possible uses: the prevention and treatment of atopic, respiratory tract, and inflammatory bowel diseases. CONCLUSIONS:better knowledge about postbiotics can be useful for the prevention and treatment of several human body diseases, alone or as an add-on to PRE-PRO-SYMB.
10.3390/ijerph19010037
COVID-19 - gastrointestinal and gut microbiota-related aspects.
Kaźmierczak-Siedlecka K,Vitale E,Makarewicz W
European review for medical and pharmacological sciences
OBJECTIVE:The aim of this review paper was to discuss the gut microbiota-related aspects of COVID-19 patients. We presented the faecal-oral transmission of SARS-CoV-2, gut microbiota imbalance, and fecal microbiota transplantation as a hidden source of this virus. MATERIALS AND METHODS:We analyzed the available literature (PubMed, Embase, Google Scholar databases) regarding COVID-19 and gut microbiota related aspects. RESULTS:The gastrointestinal symptoms, such as nausea, vomiting, diarrhea, abdominal discomfort/pain, may occur in these patients. Notably, these symptoms may contribute to the severity of COVID-19. Recent several studies have revealed a new SARS-CoV-2 transmission possibility, opening a fresh view on COVID-19. It is observed the possibility of SARS-CoV-2 transmission via faecal-oral route. Fecal microbiota transplantation may be a hidden source of SARS-CoV-2. Additionally, the pharmacological treatment of COVID-19 and other factors may significantly alter the composition of gut microbiota. Among others, loss of bacterial diversity, the decrease of commensal microbes as well as the increase of opportunistic pathogens are observed. CONCLUSIONS:The alterations of gut microbiota in COVID-19 patients consequently may lead to the development of gut dysbiosis-related diseases even after recovery from COVID-19. Therefore, it is recommended to screen stool samples taken from recovered patients at least 35 days after clearance of virus from respiratory tract. Before 35 days period, SARS-CoV-2 may still be detected in feces. It is also recommended to screen the composition as well as the activity of gut microbiota to assess its balance. In the case of gut dysbiosis, there should be introduced an appropriate method of its modulation. Additionally, all the fecal samples which are prepared for fecal microbiota transplantation should be tested for SARS-CoV-2 to provide protection for its recipients.
10.26355/eurrev_202010_23448
Role of oral and gut microbiota in childhood obesity.
Folia microbiologica
Childhood obesity not only causes damage to children's respiratory, cardiovascular, endocrine, motor, and other systems but also is a significant risk factor for metabolic diseases such as obesity in adulthood, which has become one of the serious public health problems worldwide. The etiology and pathogenesis of obesity are complex. In addition to genetic and lifestyle factors, recent studies have found that the microbes in the digestive tract play a crucial role in the occurrence and development of obesity. Among them, the gut microbiota has been confirmed to be one of the important pathogenic factors of obesity, which can mediate the occurrence and development of obesity by interfering with the balance of host energy metabolism and inducing low-grade chronic inflammation throughout the host. Targeting the gut microbiota to treat obesity through various methods such as fecal microbiota transplantation, dietary intervention, and probiotic supplementation has become a research hotspot in obesity treatment. In addition, the oral microbiota is also considered closely related to the occurrence and development of obesity due to its regulatory effect on the balance of gut microbiota. Exploring the relationship between oral and gut microbiota and childhood obesity elucidates the pathogenesis and treatment concepts of childhood obesity from a new perspective. It may provide new methods for the prevention and treatment of childhood obesity in the future.
10.1007/s12223-023-01033-3
[Lung and gut microbiota and their interaction with the carcinogenesis and development of lung cancer: a review].
Zhang Yaokun,Zhang Youming,Si Hongli
Sheng wu gong cheng xue bao = Chinese journal of biotechnology
Lung microbiota and gut microbiota are closely related to lung cancer. Studies have shown that the dysbiosis, i.e., the significantly altered composition and structure of gut and lung microbiota, usually occurs in patients with lung cancer. With the introduction of "Gut-Lung Axis", an increasing attention has been paid to the close relationship between the lung and gut microbiota in human body. A deeper insight into this relationship would facilitate understanding the mechanisms behind the carcinogenesis and development of lung cancer. This article summarizes the composition of lung and gut microbiota in patients with lung cancer and the possible interaction mechanisms, highlighting the importance of the immune system in the Gut-Lung Axis. The effects of lung and gut microbiota on the clinical treatment of lung cancer were summarized, based on which the authors propose that the lung and gut microbiota can be used as novel targets for early diagnosis and treatment of lung cancer.
10.13345/j.cjb.210081
Circadian orchestration of host and gut microbiota in infection.
Biological reviews of the Cambridge Philosophical Society
Circadian rhythms are present in almost every organism and regulate multiple aspects of biological and physiological processes (e.g. metabolism, immune responses, and microbial exposure). There exists a bidirectional circadian interaction between the host and its gut microbiota, and potential circadian orchestration of both host and gut microbiota in response to invading pathogens. In this review, we summarize what is known about these intestinal microbial oscillations and the relationships between host circadian clocks and various infectious agents (bacteria, fungi, parasites, and viruses), and discuss how host circadian clocks prime the immune system to fight pathogen infections as well as the direct effects of circadian clocks on viral activity (e.g. SARS-CoV-2 entry and replication). Finally, we consider strategies employed to realign normal circadian rhythmicity for host health, such as chronotherapy, dietary intervention, good sleep hygiene, and gut microbiota-targeted therapy. We propose that targeting circadian rhythmicity may provide therapeutic opportunities for the treatment of infectious diseases.
10.1111/brv.12898
Gut Microbiota-targeted Interventions for Reducing the Incidence, Duration, and Severity of Respiratory Tract Infections in Healthy Non-elderly Adults.
Military medicine
INTRODUCTION:Respiratory tract infections (RTI), such as those caused by influenza viruses and, more recently, the severe acute respiratory syndrome coronavirus-2, pose a significant burden to military health care systems and force readiness. The gut microbiota influences immune function, is malleable, and may provide a target for interventions aiming to reduce RTI burden. This narrative review summarizes existing evidence regarding the effectiveness of probiotics, prebiotics, and synbiotics, all of which are gut microbiota-targeted interventions, for reducing the burden of RTI in military-relevant populations (i.e., healthy non-elderly adults). MATERIALS AND METHODS:A systematic search strategy was used to identify recent meta-analyses and systematic reviews of randomized controlled trials conducted in healthy non-elderly adults which examined effects of probiotics, prebiotics, or synbiotics on the incidence, duration, and/or severity of RTI, or on immune responses to vaccinations against viruses that cause RTI. Relevant randomized controlled clinical trials not included in those reports were also identified. RESULTS:Meta-analyses and multiple randomized controlled trials have demonstrated that certain probiotic strains may reduce the incidence, duration, and/or severity of RTI and improve immune responses to vaccination against RTI-causing pathogens in various populations including healthy non-elderly adults. Fewer randomized controlled trials have examined the effects of prebiotics or synbiotics on RTI-related outcomes in healthy non-elderly adults. Nevertheless, some studies conducted within that population and other populations have observed that certain prebiotics and synbiotics reduce the incidence, duration, and/or severity of RTI or improve immune responses to vaccinations against RTI-causing viruses. However, across all product classes, not all product formulations have shown benefit, and most have not been tested in multiple randomized controlled trials in military-relevant populations. CONCLUSION:Dietary supplementation with certain gut microbiota-targeted interventions, and certain probiotics in particular, may provide viable strategies for reducing RTI-related illness in military personnel. Research in military populations is warranted to fully understand the magnitude of any military health and cost benefits, and to establish definitive recommendations for use.
10.1093/milmed/usaa261
Gut Serpinome: Emerging Evidence in IBD.
Mkaouar Héla,Mariaule Vincent,Rhimi Soufien,Hernandez Juan,Kriaa Aicha,Jablaoui Amin,Akermi Nizar,Maguin Emmanuelle,Lesner Adam,Korkmaz Brice,Rhimi Moez
International journal of molecular sciences
Inflammatory bowel diseases (IBD) are incurable disorders whose prevalence and global socioeconomic impact are increasing. While the role of host genetics and immunity is well documented, that of gut microbiota dysbiosis is increasingly being studied. However, the molecular basis of the dialogue between the gut microbiota and the host remains poorly understood. Increased activity of serine proteases is demonstrated in IBD patients and may contribute to the onset and the maintenance of the disease. The intestinal proteolytic balance is the result of an equilibrium between the proteases and their corresponding inhibitors. Interestingly, the serine protease inhibitors (serpins) encoded by the host are well reported; in contrast, those from the gut microbiota remain poorly studied. In this review, we provide a concise analysis of the roles of serine protease in IBD physiopathology and we focus on the serpins from the gut microbiota (gut serpinome) and their relevance as a promising therapeutic approach.
10.3390/ijms22116088
Probiotics and COVID-19: is there any link?
Letters in applied microbiology
Understanding mechanisms of the novel SARS-CoV2 infection and progression can provide potential novel targets for prevention and/or treatment. This could be achieved via the inhibition of viral entry and/or replication, or by suppression of the immunologic response that is provoked by the infection (known as the cytokine storm). Probiotics are defined as 'live microorganisms that, when administered in adequate amounts, confer a health benefit on the host'. There is scarcity of evidence about the relationship between COVID-19 and gut microbiota. So, whether or not these supplements can prevent or ameliorate COVID-19-associated symptoms is not fully understood. The aim of this study is to provide an indirect evidence about the utility of probiotics in combating COVID-19 or its associated symptoms, through the review of its antiviral and anti-inflammatory properties in vitro, animal models and human trials. SIGNIFICANCE AND IMPACT OF THE STUDY: The role of probiotics in alleviation of the novel COVID-19 has not been established. This review provides an insight about the anti-inflammatory, antiviral effects of probiotics in vitro, animal models and human. The latter can provide an indirect evidence and/or hypothesis-driven approach to investigate the use of probiotics as adjunctive therapy in the prophylaxis and/or alleviation of COVID-19 symptoms.
10.1111/lam.13334
Lung microbiome: an emerging player in lung cancer pathogenesis and progression.
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
The microbiome of the lungs, although until recently neglected, is now emerging as a potential contributor to chronic lung diseases, including cancer. Preclinical evidence suggests that the microbial burden of the lungs shapes the host immunity mechanisms and affects local antitumor immune responses. Studies of cohorts of patients with lung cancer reveal that different microbiome profiles are detected in patients with lung cancer compared to controls. In addition, an association between differential lung microbiome composition and distinct responses to immunotherapy has been suggested, yet, with limited data. Scarce evidence exists on the role of the lung microbiome in the development of metastases in the lungs. Interestingly, the lung microbiome is not isolated and interacts with the gut microbiome through a dynamic axis. Future research on the involvement of the lung microbiome in lung cancer pathogenesis and potential therapeutic implications is greatly anticipated.
10.1007/s12094-023-03139-z
Implications of SARS-CoV-2 infection for neurogastroenterology.
Neurogastroenterology and motility
BACKGROUND:Coronavirus disease 2019 (COVID-19) is associated with gastrointestinal and hepatic manifestation in up to one fifth of patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, infects gastrointestinal epithelial cells expressing angiotensin-converting enzyme 2 (ACE2) receptors triggering a cascade of events leading to mucosal and systemic inflammation. Symptomatic patients display changes in gut microbiota composition and function which may contribute to intestinal barrier dysfunction and immune activation. Evidence suggests that SARS-CoV-2 infection and related mucosal inflammation impact on the function of the enteric nervous system and the activation of sensory fibers conveying information to the central nervous system, which, may at least in part, contribute symptom generation such as vomiting and diarrhea described in COVID-19. Liver and pancreas dysfunctions have also been described as non-respiratory complications of COVID-19 and add further emphasis to the common view of SARS-CoV-2 infection as a systemic disease with multiorgan involvement. PURPOSE:The aim of this review was to highlight the current knowledge on the pathophysiology of gastrointestinal SARS-CoV-2 infection, including the crosstalk with the gut microbiota, the fecal-oral route of virus transmission, and the potential interaction of the virus with the enteric nervous system. We also review the current available data on gastrointestinal and liver manifestations, management, and outcomes of patients with COVID-19.
10.1111/nmo.14104
Considerations for Gut Microbiota and Probiotics in Patients with Diabetes Amidst the Covid-19 Pandemic: A Narrative Review.
Barengolts Elena,Smith Emily Daviau
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
OBJECTIVE:To review data implicating microbiota influences on Coronavirus Disease 2019 (COVID-19) in patients with diabetes. METHODS:Primary literature review included topics: "COVID-19," "SARS," "MERS," "gut micro-biota," "probiotics," "immune system," "ACE2," and "metformin." RESULTS:Diabetes was prevalent (~11%) among COVID-19 patients and associated with increased mortality (about 3-fold) compared to patients without diabetes. COVID-19 could be associated with worsening diabetes control and new diabetes diagnosis that could be linked to high expression of angiotensin-converting enzyme 2 (ACE2) receptors (coronavirus point of entry into the host) in the endocrine pancreas. A pre-existing gut microbiota imbalance (dysbiosis) could contribute to COVID-19-related complications in patients with diabetes. The COVID-19 virus was found in fecal samples (~55%), persisted for about 5 weeks, and could be associated with diarrhea, suggesting a role for gut dysbiosis. ACE2 expressed on enterocytes and colonocytes could serve as an alternative route for acquiring COVID-19. Experimental models proposed some probiotics, including Lactobacillus casei, L. plantarum, and L. salivarius, as vectors for delivering or enhancing efficacy of anti-coronavirus vaccines. These Lactobacillus probiotics were also beneficial for diabetes. The potential mechanisms for interconnections between coronavirus, diabetes, and gut microbiota could be related to the immune system, ACE2 pathway, and metformin treatment. There were suggestions but no proof supporting probiotics benefits for COVID-19 infection. CONCLUSION:The data suggested that the host environment including the gut microbiota could play a role for COVID-19 in patients with diabetes. It is a challenge to the scientific community to investigate the beneficial potential of the gut microbiota for strengthening host defense against coronavirus in patients with diabetes.
10.4158/EP-2020-0336
The Human Microbiome and Its Role in Musculoskeletal Disorders.
Genes
Musculoskeletal diseases (MSDs) are characterized as injuries and illnesses that affect the musculoskeletal system. MSDs affect every population worldwide and are associated with substantial global burden. Variations in the makeup of the gut microbiota may be related to chronic MSDs. There is growing interest in exploring potential connections between chronic MSDs and variations in the composition of gut microbiota. The human microbiota is a complex community consisting of viruses, archaea, bacteria, and eukaryotes, both inside and outside of the human body. These microorganisms play crucial roles in influencing human physiology, impacting metabolic and immunological systems in health and disease. Different body areas host specific types of microorganisms, with facultative anaerobes dominating the gastrointestinal tract (able to thrive with or without oxygen), while strict aerobes prevail in the nasal cavity, respiratory tract, and skin surfaces (requiring oxygen for development). Together with the immune system, these bacteria have coevolved throughout time, forming complex biological relationships. Changes in the microbial ecology of the gut may have a big impact on health and can help illnesses develop. These changes are frequently impacted by lifestyle choices and underlying medical disorders. The potential for safety, expenses, and efficacy of microbiota-based medicines, even with occasional delivery, has attracted interest. They are, therefore, a desirable candidate for treating MSDs that are chronic and that may have variable progression patterns. As such, the following is a narrative review to address the role of the human microbiome as it relates to MSDs.
10.3390/genes14101937
The Gut-Lung Axis in Cystic Fibrosis.
Journal of bacteriology
Cystic fibrosis (CF) is a heritable, multiorgan disease that impacts all tissues that normally express cystic fibrosis transmembrane conductance regulator (CFTR) protein. While the importance of the airway microbiota has long been recognized, the intestinal microbiota has only recently been recognized as an important player in both intestinal and lung health outcomes for persons with CF (pwCF). Here, we summarize current literature related to the gut-lung axis in CF, with a particular focus on three key ideas: (i) mechanisms through which microbes influence the gut-lung axis, (ii) drivers of microbiota alterations, and (iii) the potential for intestinal microbiota remediation.
10.1128/JB.00311-21
Salivary Biomarkers in Lung Cancer.
Mediators of inflammation
A very low percentage of lung cancer (LC) cases are discovered at an early and treatable stage of the disease, leading to an abysmally low 5-year survival rate. This underscores the immediate necessity for improved diagnostic, prognostic, and predictive biomarkers for LC. Biopsied lung tissue, blood, and plasma are common sources used for LC diagnosis and monitoring of the disease. A growing number of studies have reported saliva to be a useful biological sample for early and noninvasive detection of oral and systemic diseases. Nevertheless, salivary biomarker discovery remains underresearched. Here, we have compiled the available literature to provide an overview of the current understanding of salivary markers for LC detection and provided perspectives for future clinical significance. Valuable markers with diagnostic and prognostic potentials in LC have been discovered in saliva, including metabolic (catalase activity, triene conjugates, and Schiff bases), inflammatory (interleukin 10, C-X-C motif chemokine ligand 10), proteomic (haptoglobin, zinc--2-glycoprotein, and calprotectin), genomic (epidermal growth factor receptor), and microbial candidates ( and ). In combination, with each other and with other established screening methods, these salivary markers could be useful for improving early detection of the disease and ultimately improve the survival odds of LC patients. The existing literature suggests that saliva is a promising biological sample for identification and validation of biomarkers in LC, but how saliva can be utilized most effectively in a clinical setting for LC management is still under investigation.
10.1155/2021/6019791
Probiotics in Medicine: A Long Debate.
Frontiers in immunology
During the last years probiotics gained the attention of clinicians for their use in the prevention and treatment of multiple diseases. Probiotics main mechanisms of action include enhanced mucosal barrier function, direct antagonism with pathogens, inhibition of bacterial adherence and invasion capacity in the intestinal epithelium, boosting of the immune system and regulation of the central nervous system. It is accepted that there is a mutual communication between the gut microbiota and the liver, the so-called "microbiota-gut-liver axis" as well as a reciprocal communication between the intestinal microbiota and the central nervous system through the "microbiota-gut-brain axis." Moreover, recently the "gut-lung axis" in bacterial and viral infections is considerably discussed for bacterial and viral infections, as the intestinal microbiota amplifies the alveolar macrophage activity having a protective role in the host defense against pneumonia. The importance of the normal human intestinal microbiota is recognized in the preservation of health. Disease states such as, infections, autoimmune conditions, allergy and other may occur when the intestinal balance is disturbed. Probiotics seem to be a promising approach to prevent and even reduce the symptoms of such clinical states as an adjuvant therapy by preserving the balance of the normal intestinal microbiota and improving the immune system. The present review states globally all different disorders in which probiotics can be given. To date, Stronger data in favor of their clinical use are provided in the prevention of gastrointestinal disorders, antibiotic-associated diarrhea, allergy and respiratory infections. We hereby discuss the role of probiotics in the reduction of the respiratory infection symptoms and we focus on the possibility to use them as an adjuvant to the therapeutic approach of the pandemic COVID-19. Nevertheless, it is accepted by the scientific community that more clinical studies should be undertaken in large samples of diseased populations so that the assessment of their therapeutic potential provide us with strong evidence for their efficacy and safety in clinical use.
10.3389/fimmu.2020.02192
The lung microbiome in neonates.
Permall Dhivya Lakshmi,Pasha Asfia Banu,Chen Xiao-Qing,Lu Hong-Yan
The Turkish journal of pediatrics
Permall DL, Pasha AB, Chen XQ, Lu HY. The lung microbiome in neonates. Turk J Pediatr 2019; 61: 821-830. Despite the advent of culture-independent techniques to identify members of the microbiome, studies focusing on the lung microbiome of neonates are scarce. Understanding the role of the microbiome in the pathogenesis of pulmonary conditions affecting newborns could lead to the initiation of pioneering therapeutic interventions, which could potentially prevent lifelong disability. Bronchopulmonary dysplasia (BPD) has been associated with a less diverse microbiome, presence of Ureaplasma species and reduced Lactobacillus detection. Additionally, the potential role of microbial dysbiosis in the pathogenesis of asthma, cystic fibrosis and pneumonia has been described. There has also been a surge of interest in attempting to elucidate the interactions between the airway and gut microbiomes and their bearings on respiratory health and diseases to eventually broaden the scope of therapeutic interventions.
10.24953/turkjped.2019.06.001
Choline in cystic fibrosis: relations to pancreas insufficiency, enterohepatic cycle, PEMT and intestinal microbiota.
European journal of nutrition
BACKGROUND:Cystic Fibrosis (CF) is an autosomal recessive disorder with life-threatening organ manifestations. 87% of CF patients develop exocrine pancreas insufficiency, frequently starting in utero and requiring lifelong pancreatic enzyme substitution. 99% develop progressive lung disease, and 20-60% CF-related liver disease, from mild steatosis to cirrhosis. Characteristically, pancreas, liver and lung are linked by choline metabolism, a critical nutrient in CF. Choline is a tightly regulated tissue component in the form of phosphatidylcholine (Ptd'Cho) and sphingomyelin (SPH) in all membranes and many secretions, particularly of liver (bile, lipoproteins) and lung (surfactant, lipoproteins). Via its downstream metabolites, betaine, dimethylglycine and sarcosine, choline is the major one-carbon donor for methionine regeneration from homocysteine. Methionine is primarily used for essential methylation processes via S-adenosyl-methionine. CLINICAL IMPACT:CF patients with exocrine pancreas insufficiency frequently develop choline deficiency, due to loss of bile Ptd'Cho via feces. ~ 50% (11-12 g) of hepatic Ptd'Cho is daily secreted into the duodenum. Its re-uptake requires cleavage to lyso-Ptd'Cho by pancreatic and small intestinal phospholipases requiring alkaline environment. Impaired CFTR-dependent bicarbonate secretion, however, results in low duodenal pH, impaired phospholipase activity, fecal Ptd'Cho loss and choline deficiency. Low plasma choline causes decreased availability for parenchymal Ptd'Cho metabolism, impacting on organ functions. Choline deficiency results in hepatic choline/Ptd'Cho accretion from lung tissue via high density lipoproteins, explaining the link between choline deficiency and lung function. Hepatic Ptd'Cho synthesis from phosphatidylethanolamine by phosphatidylethanolamine-N-methyltransferase (PEMT) partly compensates for choline deficiency, but frequent single nucleotide polymorphisms enhance choline requirement. Additionally, small intestinal bacterial overgrowth (SIBO) frequently causes intraluminal choline degradation in CF patients prior to its absorption. As adequate choline supplementation was clinically effective and adult as well as pediatric CF patients suffer from choline deficiency, choline supplementation in CF patients of all ages should be evaluated.
10.1007/s00394-020-02358-2
Impact of the gut microbiota on angiotensin Ⅱ-related disorders and its mechanisms.
Biochemical pharmacology
The renin-angiotensin system (RAS) consists of multiple angiotensin peptides and performs various biological functions mediated by distinct receptors. Angiotensin II (Ang II) is the major effector of the RAS and affects the occurrence and development of inflammation, diabetes mellitus and its complications, hypertension, and end-organ damage via the Ang II type 1 receptor. Recently, considerable interest has been given to the association and interaction between the gut microbiota and host. Increasing evidence suggests that the gut microbiota may contribute to cardiovascular diseases, obesity, type 2 diabetes mellitus, chronic inflammatory diseases, and chronic kidney disease. Recent data have confirmed that Ang II can induce an imbalance in the intestinal flora and further aggravate disease progression. Furthermore, angiotensin converting enzyme 2 is another player in RAS, alleviates the deleterious effects of Ang II, modulates gut microbial dysbiosis, local and systemic immune responses associated with coronavirus disease 19. Due to the complicated etiology of pathologies, the precise mechanisms that link disease processes with specific characteristics of the gut microbiota remain obscure. This review aims to highlight the complex interactions between the gut microbiota and its metabolites in Ang II-related disease progression, and summarize the possible mechanisms. Deciphering these mechanisms will provide a theoretical basis for novel therapeutic strategies for disease prevention and treatment. Finally, we discuss therapies targeting the gut microbiota to treat Ang II-related disorders.
10.1016/j.bcp.2023.115659
Gut microbiota-derived vitamins - underrated powers of a multipotent ally in psychiatric health and disease.
Rudzki Leszek,Stone Trevor W,Maes Michael,Misiak Błażej,Samochowiec Jerzy,Szulc Agata
Progress in neuro-psychopharmacology & biological psychiatry
Despite the well-established roles of B-vitamins and their deficiencies in health and disease, there is growing evidence indicating a key role of those nutrients in functions of the central nervous system and in psychopathology. Clinical data indicate the substantial role of B-vitamins in various psychiatric disorders, including major depression, bipolar disorder, schizophrenia, autism, and dementia, including Alzheimer's and Parkinson's diseases. As enzymatic cofactors, B-vitamins are involved in many physiological processes such as the metabolism of glucose, fatty acids and amino acids, metabolism of tryptophan in the kynurenine pathway, homocysteine metabolism, synthesis and metabolism of various neurotransmitters and neurohormones including serotonin, dopamine, adrenaline, acetylcholine, GABA, glutamate, D-serine, glycine, histamine and melatonin. Those vitamins are highly involved in brain energetic metabolism and respiration at the cellular level. They have a broad range of anti-inflammatory, immunomodulatory, antioxidant and neuroprotective properties. Furthermore, some of those vitamins are involved in the regulation of permeability of the intestinal and blood-brain barriers. Despite the fact that a substantial amount of the above vitamins is acquired from various dietary sources, deficiencies are not uncommon, and it is estimated that micronutrient deficiencies affect about two billion people worldwide. The majority of gut-resident microbes and the broad range of bacteria available in fermented food, express genetic machinery enabling the synthesis and metabolism of B-vitamins and, consequently, intestinal microbiota and fermented food rich in probiotic bacteria are essential sources of B-vitamins for humans. All in all, there is growing evidence that intestinal bacteria-derived vitamins play a significant role in physiology and that dysregulation of the "microbiota-vitamins frontier" is related to various disorders. In this review, we will discuss the role of vitamins in mental health and explore the perspectives and potential of how gut microbiota-derived vitamins could contribute to mental health and psychiatric treatment.
10.1016/j.pnpbp.2020.110240
Brain-Gut-Microbiota Axis in Amyotrophic Lateral Sclerosis: A Historical Overview and Future Directions.
Aging and disease
Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease which is strongly associated with age. The incidence of ALS increases from the age of 40 and peaks between the ages of 65 and 70. Most patients die of respiratory muscle paralysis or lung infections within three to five years of the appearance of symptoms, dealing a huge blow to patients and their families. With aging populations, improved diagnostic methods and changes in reporting criteria, the incidence of ALS is likely to show an upward trend in the coming decades. Despite extensive researches have been done, the cause and pathogenesis of ALS remains unclear. In recent decades, large quantities of studies focusing on gut microbiota have shown that gut microbiota and its metabolites seem to change the evolvement of ALS through the brain-gut-microbiota axis, and in turn, the progression of ALS will exacerbate the imbalance of gut microbiota, thereby forming a vicious cycle. This suggests that further exploration and identification of the function of gut microbiota in ALS may be crucial to break the bottleneck in the diagnosis and treatment of this disease. Hence, the current review summarizes and discusses the latest research advancement and future directions of ALS and brain-gut-microbiota axis, so as to help relevant researchers gain correlative information instantly.
10.14336/AD.2023.0524
Human Microbiota Network: Unveiling Potential Crosstalk between the Different Microbiota Ecosystems and Their Role in Health and Disease.
Nutrients
The human body is host to a large number of microorganisms which conform the human microbiota, that is known to play an important role in health and disease. Although most of the microorganisms that coexist with us are located in the gut, microbial cells present in other locations (like skin, respiratory tract, genitourinary tract, and the vaginal zone in women) also play a significant role regulating host health. The fact that there are different kinds of microbiota in different body areas does not mean they are independent. It is plausible that connection exist, and different studies have shown that the microbiota present in different zones of the human body has the capability of communicating through secondary metabolites. In this sense, dysbiosis in one body compartment may negatively affect distal areas and contribute to the development of diseases. Accordingly, it could be hypothesized that the whole set of microbial cells that inhabit the human body form a system, and the dialogue between the different host microbiotas may be a contributing factor for the susceptibility to developing diseased states. For this reason, the present review aims to integrate the available literature on the relationship between the different human microbiotas and understand how changes in the microbiota in one body region can influence other microbiota communities in a bidirectional process. The findings suggest that the different microbiotas may act in a coordinated way to decisively influence human well-being. This new integrative paradigm opens new insights in the microbiota field of research and its relationship with human health that should be taken into account in future studies.
10.3390/nu13092905
The microbiome in asthma.
Huang Yvonne J,Boushey Homer A
The Journal of allergy and clinical immunology
The application of recently developed sensitive, specific, culture-independent tools for identification of microbes is transforming concepts of microbial ecology, including concepts of the relationships between the vast complex populations of microbes associated with ourselves and with states of health and disease. Although most work initially focused on the community of microbes (microbiome) in the gastrointestinal tract and its relationship to gastrointestinal disease, interest has expanded to include study of the relationships of the airway microbiome to asthma and its phenotypes and to the relationships between the gastrointestinal microbiome, development of immune function, and predisposition to allergic sensitization and asthma. Here we provide our perspective on the findings of studies of differences in the airway microbiome between asthmatic patients and healthy subjects and of studies of relationships between environmental microbiota, gut microbiota, immune function, and asthma development. In addition, we provide our perspective on how these findings suggest the broad outline of a rationale for approaches involving directed manipulation of the gut and airway microbiome for the treatment and prevention of allergic asthma.
10.1016/j.jaci.2014.11.011
Resveratrol and Gut Microbiota Synergy: Preventive and Therapeutic Effects.
International journal of molecular sciences
The role of an imbalanced high-fat diet in the pathophysiology of common chronic noncommunicable diseases has been known for years. More recently, the concept of 'gut microbiota' and the interaction between their composition and gut metabolites produced from the intake of dietary products have gained the focus of researchers, mostly from the perspective of the prevention of cardiovascular and metabolic disorders, which are still the leading cause of death globally. The aim of this work is to highlight the health benefits of the interaction between resveratrol (RSV), red grape polyphenol, and gut microbiota, through aspects of their therapeutic and preventive potentials. Since changed microbiota (mostly as a consequence of antibiotic overuse) contribute to the persistence of post ('long')-COVID-19 symptoms, these aspects will be covered too. Data were obtained from the electronic databases (MedLine/PubMed), according to specific keywords regarding the protective role of resveratrol, the gut microbiota, and their synergy. RSV exerts beneficial properties in the modulation of cardiovascular, metabolic, and post-COVID-19-related disorders. In healthy individuals, it maintains an ergogenic capacity, prevents oxidative stress, and modulates the inflammatory response. Overall, it improves quality of life. The RSV-gut-microbiota interaction is beneficial in terms of maintaining human health. Along with physical activity, it is key for the prevention of chronic noncommunicable diseases.
10.3390/ijms242417573
Gut Microbiota and Mitochondria: Health and Pathophysiological Aspects of Long COVID.
International journal of molecular sciences
The current understanding of long COVID (LC) is still limited. This review highlights key findings regarding the role of gut microbiota, mitochondria, and the main pathophysiological aspects of LC revealed by clinical studies, related to the complex interplay between infection, intestinal dysbiosis, dysfunctional mitochondria, and systemic inflammation generated in a vicious circle, reflecting the molecular and cellular processes from the "leaky gut" to the "leaky electron transport chain (ETC)" into a quantum leap. The heterogeneity of LC has hindered progress in deciphering all the pathophysiological mechanisms, and therefore, the approach must be multidisciplinary, with a special focus not only on symptomatic management but also on addressing the underlying health problems of the patients. It is imperative to further assess and validate the effects of COVID-19 and LC on the gut microbiome and their relationship to infections with other viral agents or pathogens. Further studies are needed to better understand LC and expand the interdisciplinary points of view that are required to accurately diagnose and effectively treat this heterogeneous condition. Given the ability of SARS-CoV-2 to induce autoimmunity in susceptible patients, they should be monitored for symptoms of autoimmune disease after contracting the viral infection. One question remains open, namely, whether the various vaccines developed to end the pandemic will also induce autoimmunity. Recent data highlighted in this review have revealed that the persistence of SARS-CoV-2 and dysfunctional mitochondria in organs such as the heart and, to a lesser extent, the kidneys, liver, and lymph nodes, long after the organism has been able to clear the virus from the lungs, could be an explanation for LC.
10.3390/ijms242417198
Investigation of the relationships among respiratory syncytial virus infection, T cell immune response and intestinal flora.
European review for medical and pharmacological sciences
The aim of this work was to evaluate the relationships among respiratory syncytial virus infection, T cell immune response and intestinal flora. Peer-reviewed papers published in English were collected through extensive searches performed in PubMed, Web of Science, Google Scholar, and China National Knowledge Infrastructure databases. The articles were reviewed to extract relevant information on the immune responses of Th1/Th2 and Treg/Th17 to respiratory syncytial virus infection in the body. RSV (Respiratory syncytial virus, RSV) infection leads to imbalance between Th1/Th2 and Treg/Th17 immune cells, resulting in Th2 or Th17 dominant immune responses, which can generate immune disorder and aggravate clinical symptoms. Intestinal micro-organisms play very important roles in maintaining stable immune environment, stimulating immune system maturation and balancing Th1/Th2 and Treg/Th17 immune systems in children. In our review of various papers from around the world, we speculated that the steady state of intestinal bacteria was disturbed after children got infected with RSV, resulting in intestinal flora disorder. Then, the imbalance between Th1/Th2 and Treg/Th17 immune cells was increased. Both intestinal flora disorder and RSV infection could cause cellular immunity imbalance of Th1/Th2 or Treg/Th17, eventually leading to disease deterioration and even a vicious cycle. Normal intestinal flora can maintain immune system stability, regulate the dynamic balance of Th1/Th2 and Treg/Th17 and prevent or mitigate adverse consequences of RSV infection. Because probiotics can improve intestinal barrier function and regulate immune response, they can effectively be used to treat children with recurrent respiratory tract infections. Using conventional antiviral therapy strategy supplemented with probiotics in the treatment of clinical RSV infection may be better for the body.
10.26355/eurrev_202303_31804
Probiotics, Photobiomodulation, and Disease Management: Controversies and Challenges.
Ailioaie Laura Marinela,Litscher Gerhard
International journal of molecular sciences
In recent decades, researchers around the world have been studying intensively how micro-organisms that are present inside living organisms could affect the main processes of life, namely health and pathological conditions of mind or body. They discovered a relationship between the whole microbial colonization and the initiation and development of different medical disorders. Besides already known probiotics, novel products such as postbiotics and paraprobiotics have been developed in recent years to create new non-viable micro-organisms or bacterial-free extracts, which can provide benefits to the host with additional bioactivity to probiotics, but without the risk of side effects. The best alternatives in the use of probiotics and postbiotics to maintain the health of the intestinal microbiota and to prevent the attachment of pathogens to children and adults are highlighted and discussed as controversies and challenges. Updated knowledge of the molecular and cellular mechanisms involved in the balance between microbiota and immune system for the introspection on the gut-lung-brain axis could reveal the latest benefits and perspectives of applied photobiomics for health. Multiple interconditioning between photobiomodulation (PBM), probiotics, and the human microbiota, their effects on the human body, and their implications for the management of viral infectious diseases is essential. Coupled complex PBM and probiotic interventions can control the microbiome, improve the activity of the immune system, and save the lives of people with immune imbalances. There is an urgent need to seek and develop innovative treatments to successfully interact with the microbiota and the human immune system in the coronavirus crisis. In the near future, photobiomics and metabolomics should be applied innovatively in the SARS-CoV-2 crisis (to study and design new therapies for COVID-19 immediately), to discover how bacteria can help us through adequate energy biostimulation to combat this pandemic, so that we can find the key to the hidden code of communication between RNA viruses, bacteria, and our body.
10.3390/ijms22094942
The intersect of genetics, environment, and microbiota in asthma-perspectives and challenges.
Tang Howard H F,Teo Shu Mei,Sly Peter D,Holt Patrick G,Inouye Michael
The Journal of allergy and clinical immunology
In asthma, a significant portion of the interaction between genetics and environment occurs through microbiota. The proposed mechanisms behind this interaction are complex and at times contradictory. This review covers recent developments in our understanding of this interaction: the "microbial hypothesis" and the "farm effect"; the role of endotoxin and genetic variation in pattern recognition systems; the interaction with allergen exposure; the additional involvement of host gut and airway microbiota; the role of viral respiratory infections in interaction with the 17q21 and CDHR3 genetic loci; and the importance of in utero and early-life timing of exposures. We propose a unified framework for understanding how all these phenomena interact to drive asthma pathogenesis. Finally, we point out some future challenges for continued research in this field, in particular the need for multiomic integration, as well as the potential utility of asthma endotyping.
10.1016/j.jaci.2020.08.026
Exploring the potential relationships among obstructive sleep apnea, erectile dysfunction, and gut microbiota: a narrative review.
Sexual medicine reviews
INTRODUCTION:Poor sleep quality is closely associated with comorbidities affecting a multitude of organ systems. Among the sleep disorders in the population, there has recently been an increase in the prevalence of obstructive sleep apnea (OSA), which has particularly affected men. The intermittent hypoxia and sleep fragmentation associated with OSA can result in the manifestation or aggravation of a number of pathophysiologic conditions, including the impairment of reproductive function in men and women. In this context, erectile dysfunction (ED) is of particular concern. Other consequences of OSA are changes in the gastrointestinal microbiota, with the resultant dysbiosis having potentially harmful consequences that promote downstream exacerbation of various comorbidities. OBJECTIVES:This narrative review aims to explore the potential relationships among ED, gut microbiota, and OSA. METHODS:A search of the relevant literature was performed in the PubMed, Embase, Medline, and Web of Science databases. RESULTS:Sleep is important for regulating the body's functions, and sleep deprivation can negatively affect health. OSA can damage organic functions, including reproductive function, and can lead to ED. Restoring the microbiota and improving sleep can help to improve sexual function or reverse ED and enhance other associated conditions mediated through the gut-brain axis relationship. Probiotics and prebiotics can be used as supportive strategies in the prevention and treatment of OSA, as they help to reduce systemic inflammation and improve intestinal barrier function. CONCLUSION:A good diet, a healthy lifestyle, and proper bowel function are essential in controlling depression and several other pathologies. Modulating the gut microbiota through probiotics and prebiotics can provide a viable strategy for developing new therapeutic options in treating many conditions. A better understanding of these a priori unrelated phenomena would foster our understanding of the effects of OSA on human fertility and how changes in gut microbiota may play a role.
10.1093/sxmrev/qead026
Intestinal Microbiota-A Promising Target for Antiviral Therapy?
Yang Mengling,Yang Yang,He Qingnan,Zhu Ping,Liu Mengqi,Xu Jiahao,Zhao Mingyi
Frontiers in immunology
The intestinal microbiota is thought to be an important biological barrier against enteric pathogens. Its depletion, however, also has curative effects against some viral infections, suggesting that different components of the intestinal microbiota can play both promoting and inhibitory roles depending on the type of viral infection. The two primary mechanisms by which the microbiota facilitates or inhibits viral invasion involve participation in the innate and adaptive immune responses and direct or indirect interaction with the virus, during which the abundance and composition of the intestinal microbiota might be changed by the virus. Oral administration of probiotics, faecal microbiota transplantation (FMT), and antibiotics are major therapeutic strategies for regulating intestinal microbiota balance. However, these three methods have shown limited curative effects in clinical trials. Therefore, the intestinal microbiota might represent a new and promising supplementary antiviral therapeutic target, and more efficient and safer methods for regulating the microbiota require deeper investigation. This review summarizes the latest research on the relationship among the intestinal microbiota, anti-viral immunity and viruses and the most commonly used methods for regulating the intestinal microbiota with the goal of providing new insight into the antiviral effects of the gut microbiota.
10.3389/fimmu.2021.676232
Role of the gut microbiota in airway immunity and host defense against respiratory infections.
Biological chemistry
Colonization of the intestine with commensal bacteria is known to play a major role in the maintenance of human health. An altered gut microbiome is associated with various ensuing diseases including respiratory diseases. Here, we summarize current knowledge on the impact of the gut microbiota on airway immunity with a focus on consequences for the host defense against respiratory infections. Specific gut commensal microbiota compositions and functions are depicted that mediate protection against respiratory infections with bacterial and viral pathogens. Lastly, we highlight factors that have imprinting effects on the establishment of the gut microbiota early in life and are potentially relevant in the context of respiratory infections. Deepening our understanding of these relationships will allow to exploit the knowledge on how gut microbiome maturation needs to be modulated to ensure lifelong enhanced resistance towards respiratory infections.
10.1515/hsz-2021-0281
The gut-lung axis in influenza A: the role of gut microbiota in immune balance.
Frontiers in immunology
Influenza A, the most common subtype, induces 3 to 5 million severe infections and 250,000 to 500,000 deaths each year. Vaccination is traditionally considered to be the best way to prevent influenza A. Yet because the Influenza A virus (IAV) is highly susceptible to antigenic drift and Antigenic shift, and because of the lag in vaccine production, this poses a significant challenge to vaccine effectiveness. Additionally, much information about the resistance of antiviral drugs, such as Oseltamivir and Baloxavir, has been reported. Therefore, the search for alternative therapies in the treatment of influenza is warranted. Recent studies have found that regulating the gut microbiota (GM) can promote the immune effects of anti-IAV via the gut-lung axis. This includes promoting IAV clearance in the early stages of infection and reducing inflammatory damage in the later stages. In this review, we first review the specific alterations in GM observed in human as well as animal models regarding IAV infection. Then we analyzed the effect of GM on host immunity against IAV, including innate immunity and subsequent adaptive immunity. Finally, our study also summarizes the effects of therapies using probiotics, prebiotics, or herbal medicine in influenza A on intestinal microecological composition and their immunomodulatory effects against IAV.
10.3389/fimmu.2023.1147724
Microbes, helminths, and rheumatic diseases.
Best practice & research. Clinical rheumatology
There has been a progressive interest on modifications of the human defense system following insults occurring in the interface between our body and the external environment, as they may provoke or worsen disease states. Studies suggest that billions of germs, which compose the gut microbiota influence one's innate and adaptive immune responses at the intestinal level, but these microorganisms may also impact rheumatic diseases. The microbiota of the skin, respiratory, and urinary tracts may also be relevant in rheumatology. Evidence indicates that changes in the gut microbiome alter the pathogenesis of immune-mediated diseases such as rheumatoid arthritis and ankylosing spondylitis but also of other disorders like atherosclerosis and osteoarthritis. Therapeutic strategies to modify the microbiota, including probiotics and fecal microbiota transplantation, have been received with skepticism, which, in turn, has drawn attention back to previously developed interventions such as antibiotics. Helminths adapted to humans over the evolution process, but their role in disease modulation, particularly immune-mediated diseases, remains to be understood. The present review focuses on data concerning modifications of the immune system induced by interactions with microbes and pluricellular organisms, namely helminths, and their impact on rheumatic diseases. Practical aspects, including specific microbiota-targeted therapies, are also discussed.
10.1016/j.berh.2020.101528
Regulation of immune function in healthy adults: one-stop guide on the role of dietary fatty acids, gut microbiota-derived short chain fatty acids, and select micronutrients in combination with physical activity.
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme
The immune system requires an adequate supply of nutrients, although current dietary recommendations may not account for optimal immune function in healthy adults. Nutrient inadequacies due to the growing influence of the western diet pose a risk for immune dysfunction. This review aims to determine the beneficial effects of supplementing dietary fats, nutrients that modulate gut microbiota, and specific micronutrients on systemic immune functions (concentrations of plasma cytokines, antibodies, and acute phase proteins) during health and acute inflammatory conditions, including COVID-19. We discussed micronutrients (selenium, zinc, and vitamin D) with compelling evidence supporting immunomodulatory properties. Additionally, the synergistic effects of physical activity and dietary interventions on systemic immune markers are explored. Briefly, evidence suggests that dietary consumption of monounsaturated (oleic and palmitoleic acids) and omega-3 polyunsaturated fatty acids (eicosapentaenoic and docosahexaenoic acids) promotes anti-inflammatory properties. Food sources (fiber, prebiotics, probiotics, omega-3) and patterns (Mediterranean diet) increase the production of short-chain fatty acids, beneficially altering gut microbiota composition, which subsequently enhances the immunomodulatory properties of circulating immune cells. A positive synergistic role of nutrient supplementation (omega-3 and fiber) and physical activity on circulating C-reactive protein and interleukin-6 levels has been observed. Lastly, omega-3 supplementation during COVID-19 infection may reduce circulating C-reactive protein and pro-inflammatory cytokines and improves pain and fatigue symptoms. This review highlights recent findings that support the beneficial role of specific nutrients in promoting systemic immune function in healthy adults. However, to establish specific dietary recommendations to support optimal immune function, more research is required. Increasing dietary fats (fish and olive oils) and specific micronutrients may positively impact systemic immune function in healthy adults. Evidence suggests that these nutrients promote immunomodulatory properties useful in resolving acute infection.
10.1139/apnm-2022-0456
Gastrointestinal Involvement in SARS-CoV-2 Infection.
Viruses
SARS-CoV-2 has evolved into a virus that primarily results in mild or asymptomatic disease, making its transmission more challenging to control. In addition to the respiratory tract, SARS-CoV-2 also infects the digestive tract. Some gastrointestinal symptoms occur with or before respiratory symptoms in patients with COVID-19. Respiratory infections are known to cause intestinal immune impairment and gastrointestinal symptoms. When the intestine is inflamed, cytokines affect the lung immune response and inflammation through blood circulation. The gastrointestinal microbiome may be a modifiable factor in determining the risk of SARS-CoV-2 infection and disease severity. The development of oral SARS-CoV-2 vaccine candidates and the maintenance of gut microbiota profiles may contribute to the early control of COVID-19 outbreaks. To this end, this review summarizes information on the gastrointestinal complications caused by SARS-CoV-2, SARS-CoV-2 infection, the gastrointestinal-lung axis immune response, potential control strategies for oral vaccine candidates and maintaining intestinal microbiota homeostasis.
10.3390/v14061188
COVID-19 and gut immunomodulation.
World journal of gastroenterology
The disease coronavirus disease 2019 (COVID-19) is a severe respiratory illness that has emerged as a devastating health problem worldwide. The disease outcome is heterogeneous, and severity is likely dependent on the immunity of infected individuals and comorbidities. Although symptoms of the disease are primarily associated with respiratory problems, additional infection or failure of other vital organs are being reported. Emerging reports suggest a quite common co-existence of gastrointestinal (GI) tract symptoms in addition to respiratory symptoms in many COVID-19 patients, and some patients show just the GI symptoms. The possible cause of the GI symptoms could be due to direct infection of the epithelial cells of the gut, which is supported by the fact that (1) The intestinal epithelium expresses a high level of angiotensin-converting enzyme-2 and transmembrane protease serine 2 protein that are required for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into the cells; (2) About half of the severe COVID-19 patients show viral RNA in their feces and various parts of the GI tract; and (3) SARS-CoV-2 can directly infect gut epithelial cells (gut epithelial cells and organoids) and (rhesus monkey). The GI tract seems to be a site of active innate and adaptive immune responses to SARS-CoV-2 as clinically, stool samples of COVID-19 patients possess proinflammatory cytokines (interleukin 8), calprotectin (neutrophils activity), and immunoglobulin A antibodies. In addition to direct immune activation by the virus, impairment of GI epithelium integrity can evoke immune response under the influence of systemic cytokines, hypoxia, and changes in gut microbiota (dysbiosis) due to infection of the respiratory system, which is confirmed by the observation that not all of the GI symptomatic patients are viral RNA positive. This review comprehensively summarizes the possible GI immunomodulation by SARS-CoV-2 that could lead to GI symptoms, their association with disease severity, and potential therapeutic interventions.
10.3748/wjg.v27.i46.7925
Modulation of gut microbiota protects against viral respiratory tract infections: a systematic review of animal and clinical studies.
European journal of nutrition
BACKGROUND:Earlier studies suggest that probiotics have protective effects in the prevention of respiratory tract infections (RTIs). Whether such benefits apply to RTIs of viral origin and mechanisms supporting the effect remain unclear. AIM:To determine the role of gut microbiota modulation on clinical and laboratory outcomes of viral RTIs. METHODS:We conducted a systematic review of articles published in Embase and MEDLINE through 20 April 2020 to identify studies reporting the effect of gut microbiota modulation on viral RTIs in clinical studies and animal models. The incidence of viral RTIs, clinical manifestations, viral load and immunological outcomes was evaluated. RESULTS:We included 58 studies (9 randomized controlled trials; 49 animal studies). Six of eight clinical trials consisting of 726 patients showed that probiotics administration was associated with a reduced risk of viral RTIs. Most commonly used probiotics were Lactobacillus followed by Bifidobacterium and Lactococcus. In animal models, treatment with probiotics before viral challenge had beneficial effects against influenza virus infection by improving infection-induced survival (20/22 studies), mitigating symptoms (21/21 studies) and decreasing viral load (23/25 studies). Probiotics and commensal gut microbiota exerted their beneficial effects through strengthening host immunity. CONCLUSION:Modulation of gut microbiota represents a promising approach against viral RTIs via host innate and adaptive immunity regulation. Further research should focus on next generation probiotics specific to viral types in prevention and treatment of emerging viral RTIs.
10.1007/s00394-021-02519-x
Microbiota-targeted therapies in inflammation resolution.
Seminars in immunology
Gut microbiota has been shown to systemically shape the immunological landscape, modulate homeostasis and play a role in both health and disease. Dysbiosis of gut microbiota promotes inflammation and contributes to the pathogenesis of several major disorders in gastrointestinal tract, metabolic, neurological and respiratory diseases. Much effort is now focused on understanding host-microbes interactions and new microbiota-targeted therapies are deeply investigated as a means to restore health or prevent disease. This review details the immunoregulatory role of the gut microbiota in health and disease and discusses the most recent strategies in manipulating individual patient's microbiota for the management and prevention of inflammatory conditions.
10.1016/j.smim.2022.101599
Interaction between gut microbiota and COVID-19 and its vaccines.
World journal of gastroenterology
The whole world has been continuously afflicted by the coronavirus disease 2019 (COVID-19) pandemic for the past 3 years. Many countries have tried many methods to control this virus infection with varying successes and failures. The gut microbiota is a biosystem spanning the entire length of the digestive tract and playing important roles in health and disease. It is much affected by COVID-19. In return it also substantially impacts infection. In particular, the gut microbiota has established a bidirectional interaction with the COVID-19 vaccines, enhancing or reducing vaccine efficacy by virtue of its varying components. Conversely, COVID-19 vaccines also make a substantial impact on the gut microbiota, re-ducing its overall population and biodiversity. It is hoped that by exploring and harnessing this bidirectional interaction we may break new ground and develop new methods to prevent and treat this formidable virus infection.
10.3748/wjg.v28.i40.5801
Paediatric COVID-19 and the GUT.
Indian journal of medical microbiology
Although children with novel coronavirus infection (COVID-19) typically present with fever and respiratory symptoms, some children have reported gastrointestinal (GI) symptoms including vomiting and diarrhoea during the course of the disease. The continuous positive detection of the viral RNA from faeces in children even after nasopharyngeal swabs turned negative suggests that the GI tract may shed virus and a tentative faecal-oral transmission. The presence of angiotensin-converting enzyme 2 receptor and transmembrane serine protease 2, which are the key proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry process, in the GI tract can explain the digestive symptoms in COVID-19. COVID-19 has implications for the management of children with chronic luminal diseases. There is increasing concern regarding the risk that children with inflammatory bowel disease being infected with SARS-CoV-2.
10.4103/ijmm.IJMM_20_331
Gut Microbiota and Lung Injury.
Tan Ji-Yang,Tang Yi-Chun,Huang Jie
Advances in experimental medicine and biology
Gut microbiota are known to impact multiple organs including the lung. The cross talk between gut microbes and lungs, termed as the "gut-lung axis," is vital for immune response and homeostasis in the airways. In this chapter, we summarized the coordinated development of microorganisms in the gut and lung, exogenous and endogenous factors related to the cross talk, the mechanisms of the gut-lung axis and their dysbiosis in lung diseases. Although the current understanding of the gut-lung axis is in its infancy, several gut microbiota-associated strategies have been designed to treat and prevent lung diseases.
10.1007/978-981-15-2385-4_5
[Intestinal microbiota, nutrients and probiotics viewed from the «gut-lung» axis].
Zolnikova O Yu,Ivaschkin K V,Bueverova E L,Ivaschkin V T
Voprosy pitaniia
Disturbance of the bronchopulmonary system are among the most common and socially significant diseases, so, the prevention and treatment of these disorders are the priority tasks of practical health care. Being based on the accumulated literature data on the interaction of the intestinal microflora and respiratory tract, the role of symbiotic bacteria of the intestinal biotope has been discussed in the respiratory diseases' pathogenesis. of the work was to analyze the results of experimental and clinical studies confirming the effect of intestinal microflora on the development and progression of respiratory diseases. The analysis of the available data on the risk reducing of occurrence, duration and severity of symptoms of bronchial asthma when taking probiotics, both in childhood and in the adult population, has been carried out. The effectiveness of the probiotic microorganisms' intake for the treatment of chronic obstructive pulmonary disease, pneumonia, viral infection, cystic fibrosis, and lung cancer has been analyzed. The main possible molecular mechanisms of the symbiotic bacteria prevention of the bronchopulmonary diseases development have been discussed in the article. . The probiotics usage in the complex treatment of bronchopulmonary diseases demonstrates encouraging results. Its potential may be useful in the treatment of various lung diseases. However, a number of questions have been related to the individual selection of specific strains, the dosage and duration of use to achieve sustained remission for a patient.
10.24411/0042-8833-2019-10025
Microbiome-focused asthma management strategies.
Shukla Shakti D,Shastri Madhur D,Chong Wai Chin,Dua Kamal,Budden Kurtis F,Mahmood Malik Quasir,Hansbro Nicole G,Keely Simon,Eri Rajaraman,Patel Rahul P,Peterson Gregory M,Hansbro Philip M
Current opinion in pharmacology
Asthma is a common, heterogeneous and serious disease with high prevalence globally. Poorly controlled, steroid-resistant asthma is particularly important as there are no effective therapies and it exerts substantial healthcare and societal burden. The role of microbiomes, particularly in chronic diseases has generated considerable interest in recent times. Existing evidence clearly demonstrates an association between asthma initiation and the microbiome, both respiratory and gastro-intestinal, although its' roles are poorly understood when assessing the asthma progression or heterogeneity (i.e. phenotypes/endotypes) across different geographical locations. Moreover, modulating microbiomes could be preventive and/or therapeutic in patients with asthma warrants urgent attention. Here, we review recent advances in assessing the role of microbiomes in asthma and present the challenges associated with the potential therapeutic utility of modifying microbiomes in management.
10.1016/j.coph.2019.06.003
Multi-kingdom gut microbiota analyses define COVID-19 severity and post-acute COVID-19 syndrome.
Nature communications
Our knowledge of the role of the gut microbiome in acute coronavirus disease 2019 (COVID-19) and post-acute COVID-19 is rapidly increasing, whereas little is known regarding the contribution of multi-kingdom microbiota and host-microbial interactions to COVID-19 severity and consequences. Herein, we perform an integrated analysis using 296 fecal metagenomes, 79 fecal metabolomics, viral load in 1378 respiratory tract samples, and clinical features of 133 COVID-19 patients prospectively followed for up to 6 months. Metagenomic-based clustering identifies two robust ecological clusters (hereafter referred to as Clusters 1 and 2), of which Cluster 1 is significantly associated with severe COVID-19 and the development of post-acute COVID-19 syndrome. Significant differences between clusters could be explained by both multi-kingdom ecological drivers (bacteria, fungi, and viruses) and host factors with a good predictive value and an area under the curve (AUC) of 0.98. A model combining host and microbial factors could predict the duration of respiratory viral shedding with 82.1% accuracy (error ± 3 days). These results highlight the potential utility of host phenotype and multi-kingdom microbiota profiling as a prognostic tool for patients with COVID-19.
10.1038/s41467-022-34535-8
Pediatric allergic rhinitis with functional gastrointestinal disease: Associations with the intestinal microbiota and gastrointestinal peptides and therapeutic effects of interventions.
Hu B,Kuang Y,Jing Y,Li Y,Zhao H,Ouyang H
Human & experimental toxicology
Children are susceptible to allergic rhinitis (caused by external allergens) accompanied by functional gastrointestinal disease, which seriously affects physical and mental health. Antihistamines and nasal spray hormones are commonly used in clinical treatment, but these drugs often have unsatisfactory efficacy and result in high recurrence rates. Therefore, understanding the pathogenesis of allergic rhinitis with functional gastrointestinal disease and seeking safer treatment and prevention methods is essential. Herein, molecular ecology and immunoassays were used to analyze correlations between pediatric allergic rhinitis with functional gastrointestinal disease and both the intestinal microbiota and gastrointestinal peptide levels. Fifty healthy children (healthy group) and 80 children with allergic rhinitis with functional gastrointestinal disease (case group: evenly divided into a control group (conventional drug therapy) and an intervention group (conventional drug therapy + glutamine+probiotics)), were enrolled. and counts and the gastrin and motilin levels were lower in the case group than in the healthy group, whereas , yeast, and counts and the somatostatin, serotonin, and vasoactive intestinal peptide levels were higher. Post treatment, intestinal microbiota indices, gastrointestinal peptide levels, and intestinal barrier function were better in the intervention group than in the control group ( < 0.05). The intervention group had a significantly higher total therapeutic response rate (95.00%) than the control group (77.50%). The intestinal microbiota was closely associated with gastrointestinal peptide levels. Treatment with glutamine and probiotics regulated these levels, re-established balance in the intestinal microbiota, and restored intestinal barrier function.
10.1177/09603271211017325
Gastrointestinal microbiome of ARDS patients induces neuroinflammation and cognitive impairment in mice.
Journal of neuroinflammation
BACKGROUND:Acute respiratory distress syndrome (ARDS) is a respiratory failure syndrome that can cause many complications, impacting patients' quality of life. Behavioral and cognitive disorders have attracted increasing attention in patients with ARDS, but its potential mechanisms are still elusive. METHODS:Herein we transferred the faecal microbiota from patients with ARDS caused by community-acquired pneumonia (CAP) to antibiotics-treated recipient male mice to explore the microbiota-gut-brain mechanisms. Behavioral functions of mice were evaluated by the open field test, Morris water maze and Y-maze test. The structure and composition of the gut microbiota were analyzed by using 16S rRNA sequencing analysis. Microglia, astrocyte and neuron in the cortex and hippocampus were examined via immunofluorescent staining. RESULTS:We found that the major characteristic of the intestinal flora in ARDS/CAP patients was higher abundances of Gram-negative bacteria than normal controls. The gut microbiota derived from ARDS/CAP patients promoted neuroinflammation and behavioral dysfunctions in mice. Mice who underwent fecal transplant from ARDS/CAP patients had increased systemic lipopolysaccharide (LPS), systemic inflammation, and increased colonic barrier permeability. This may adversely impact blood barrier permeability and facilitate microglia activation, astrocyte proliferation, and loss of neurons. CONCLUSIONS:Our study proposes the role of the microbiota-gut-brain crosstalk on ARDS/CAP-associated behavioral impairments and suggests the gut microbiota as a potential target for the protection of brain health in ARDS patients in clinical practice.
10.1186/s12974-023-02825-7
Association between the intestinal microbiota and allergic sensitization, eczema, and asthma: A systematic review.
Zimmermann Petra,Messina Nicole,Mohn William W,Finlay B Brett,Curtis Nigel
The Journal of allergy and clinical immunology
The intestinal microbiota plays an important role in development of the immune system and regulation of immune responses. This review summarizes the association between the intestinal microbiota and the development of allergic sensitization, eczema, and asthma in neonates and children. Overall, a greater relative abundance of Bacteroidaceae, Clostridiaceae, and Enterobacteriaceae and a lower relative abundance of Bifidobacteriaceae and Lactobacillaceae is associated with the development of allergic sensitization, eczema, or asthma. Reduced bacterial diversity can be associated with the development of allergic disease. The association between the composition of the intestinal microbiota and the development of allergic disease or asthma is less consistent in older children than in neonates, suggesting that early-life microbial exposure plays a more important role. Inconsistencies in the results reported from different studies might partly be explained by heterogeneity in design, study populations, diagnostic criteria, microbiota analysis methods, and reporting on different taxonomic levels. Larger studies that better account for antenatal and postnatal factors will further help determine specific microbial intestinal signatures associated with increased risk of allergy and asthma. This will enable the early identification of infants at high risk and facilitate novel strategies and interventions to prevent and treat these conditions, including modifying the intestinal microbiota early in life.
10.1016/j.jaci.2018.09.025
Gut microbiota regulate migration of lymphocytes from gut to lung.
Microbial pathogenesis
The community of microorganisms known as gut microbiota that lives in the intestine confers significant health benefits on its host, primarily in the form of immunological homeostasis regulation. Gut microbiota not only can shape immune responses in the gut but also in other organs. This review focus on the gut-lung axis. Aberrant gut microbiota development is associated with greater lung disease susceptibility and respiratory disease induced by a variety of pathogenic bacteria. They are known to cause changes in gut microbiota. Recent research has found that immune cells in the intestine migrate to distant lung to exert anti-infective effects. Moreover, evidence indicates that the gut microbiota and their metabolites influence intestinal immune cells. Therefore, we suspect that intestine-derived immune cells may play a significant role against pulmonary pathogenic infections by receiving instructions from gut microbiota.
10.1016/j.micpath.2023.106311
Early Life Exposure to Human Milk Oligosaccharides Reduces Allergic Response in a Murine Asthma Model.
Journal of immunology research
Background:Studies suggest that early-life gut microbiota composition and intestinal short-chain fatty acids (SCFAs) are linked to future asthma susceptibility. Furthermore, infancy offers a critical time window to modulate the microbiota and associated metabolites through diet-microbe interactions to promote infant health. Human milk oligosaccharides (HMOs), nondigestible carbohydrates abundant in breast milk, are prebiotics selectively metabolized by gut microbiota that consequently modify microbiome composition and SCFA production. Methods:Using a house dust mite mouse model of allergy, we investigated the impacts of early oral treatment of pups with biologically relevant doses of 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL), two of the most abundant HMOs in human milk, in amelioration of allergic airway disease severity. Results:We found that administration of 2'-FL and 6'-SL during early life reduced lung histopathology scores, circulating IgE, cytokine levels, and inflammatory cell infiltration, all hallmark symptoms of allergic asthma. HMO supplementation also increased the relative abundance of intestinal and , known SCFA producers within the gut. Indeed, we detected increased SCFA concentrations in both the intestine and blood of adult mice who received HMOs prior to weaning. Conclusion:We propose a model in which orally administered HMOs delivered during early life shift the microbiota toward increased production of SCFAs, which dampens the allergic immune responses behind allergy and asthma. Overall, these data suggest the potential for HMO supplementation to protect infants against asthma development later in life, with possible benefits against additional atopic diseases such as eczema and food allergies.
10.1155/2023/9603576
Gut microbiota and bronchopulmonary dysplasia.
Yang Kun,He Shasha,Dong Wenbin
Pediatric pulmonology
Bronchopulmonary dysplasia is a relatively common and severe complication of prematurity, and its pathogenesis remains ambiguous. Revolutionary advances in microbiological analysis techniques, together with the growing sophistication of the gut-lung axis hypothesis, have resulted in more studies linking gut microbiota dysbiosis to the occurrence and development of bronchopulmonary dysplasia. The present article builds on current findings to examine the intrinsic associations between gut microbiota and bronchopulmonary dysplasia. Gut microbiota dysbiosis may insult the intestinal barrier, triggering inflammation, metabolic disturbances, and malnutrition, consequences of which might impact bronchopulmonary dysplasia by altering the gut-lung axis. By evaluating the potential mechanisms, new therapeutic targets and potential therapeutic modalities for bronchopulmonary dysplasia can be identified from a microecological perspective.
10.1002/ppul.25508
The Intestinal Microbiota Plays as a Protective Regulator Against Radiation Pneumonitis.
Nie Xiaoqi,Li Long,Yi Minxiao,Qin Wan,Zhao Weiheng,Li Fang,Wu Bili,Yuan Xianglin
Radiation research
Radiation pneumonitis is a common complication of thoracic irradiation for lung cancer patients. The healthy gut microbiota plays an important role in the local mucosal defense process as well as pulmonary immunomodulation of the host. However, the effect of the intestinal microbiota on radiation pneumonitis is not well understood. Here we studied how the intestinal microbiota affected the host response to radiation pneumonitis. C57BL/6 mice were administered antibiotics to induce disequilibrium in the gut microbiota, and subsequently irradiated. We found that the intestinal microbiota served as a protective mediator against radiation pneumonitis, as indicated by decreased body weight and increased mortality in antibiotic-treated mice. In mice with gut microbiota disequilibrium, more serious pathological lung damage was observed at two and four weeks postirradiation. Fecal microbiota transplantation into irradiated mice led to improvement from radiation-induced inflammation two weeks postirradiation. High-throughput sequencing of murine feces displayed conversion of flora diversity, bacterial composition and community structure in the absence of normal intestinal flora. We filtered the potentially important species among the gut microbiota and considered that the tissue-type plasminogen activator might be involved in the inflammatory process. This study reveals that the gut microbiota functions as a protective regulator against radiation pneumonitis. Additionally, fecal microbiota transplantation was shown to alleviate lung injury in the irradiated model. The protective role of the healthy gut microbiota and the utilization of the gut-lung axis show potential for innovative therapeutic strategies in radiation-induced lung injury.
10.1667/RR15579.1
The Relationship between Gut Microbiota and Respiratory Tract Infections in Childhood: A Narrative Review.
Nutrients
Respiratory tract infections (RTIs) are common in childhood and represent one of the main causes of hospitalization in this population. In recent years, many studies have described the association between gut microbiota (GM) composition and RTIs in animal models. In particular, the "inter-talk" between GM and the immune system has recently been unveiled. However, the role of GM in human, and especially infantile, RTIs has not yet been fully established. In this narrative review we provide an up-to-date overview of the physiological pathways that explain how the GM shapes the immune system, potentially influencing the response to common childhood respiratory viral infections and compare studies analysing the relationship between GM composition and RTIs in children. Most studies provide evidence of GM dysbiosis, but it is not yet possible to identify a distinct bacterial signature associated with RTI predisposition. A better understanding of GM involvement in RTIs could lead to innovative integrated GM-based strategies for the prevention and treatment of RTIs in the paediatric population.
10.3390/nu14142992
[COVID-19-associated diarrhea].
Voprosy pitaniia
In addition to the typical clinical picture of respiratory symptoms and intoxication, the SARS-CoV-2 virus is also characterized by a gastroenterotropic effect. Diarrhea is one of the most common gastroenterological symptoms of COVID-19 and is detected, according to the various authors, in 2-49.5% of cases, including children. The presence of diarrhea aggravates the patient's clinical condition, limits the possibility of carrying out the necessary diagnostic manipulations, and complicates the selection of therapy. The article provides an overview of the scientific literature on the formation of diarrheal syndrome in patients with COVID-19. . Analysis of scientific publications studying the pathogenesis, incidence, clinical features, aspects of diagnosis and therapy of diarrhea in patients with COVID-19. . A search was made for scientific publications on the electronic resources PubMed, Google Scholar and eLIBRARY.ru. . The pathogenesis of diarrhea in a new coronavirus infection is complex and includes, among other things, the effect of the virus on the angiotensin-converting enzyme 2 receptors, inducing an inflammatory process in the gastrointestinal tract mucosa, neurotropic effect on the autonomic regulation of intestinal motor activity, disturbance of the colon microbiota, liver and pancreas damage. Another important pathogenetic aspect of diarrhea in COVID-19 is iatrogenic one, i.e. a side effect of drugs used in the treatment of a new coronavirus infection and its complications, and the activation of opportunistic clostridial intestinal flora against the background of antibiotic therapy. The variety of pathogenetic mechanisms of diarrheal syndrome formation allows us to speak of "COVID-associated diarrhea" as an independent clinical phenomenon characteristic for the new coronavirus infection. Mandatory diagnostic algorithm of a patient with COVID-19 and diarrhea is the fecal analysis test for toxins Cl. difficile, while the possibility of endoscopic examinations during the pandemic is limited. Compliance with the hygiene measures, diet correction and nutritional support, rational antibiotic therapy of COVID-19 complications, careful use of antiperistaltic antidiarrheal drugs, nonspecific therapy (antiviral, rehydration, adsorbents) are considered as the main therapeutic approaches for diarrheal syndrome against the background of COVID-19. The administration of probiotics and antibacterials should be considered in case of confirmed clostridial co-infection. . Diarrhea is a frequent clinical manifestation of COVID-19 and can affect the course of the disease. The complex genesis of diarrheal syndrome requires further study of therapeutic strategies and nutritional support for patients after COVID-19.
10.33029/0042-8833-2021-90-6-18-30
Pulmonary Arterial Hypertension Patients Have a Proinflammatory Gut Microbiome and Altered Circulating Microbial Metabolites.
American journal of respiratory and critical care medicine
Inflammation drives pulmonary arterial hypertension (PAH). Gut dysbiosis causes immune dysregulation and systemic inflammation by altering circulating microbial metabolites; however, little is known about gut dysbiosis and microbial metabolites in PAH. To characterize the gut microbiome and microbial metabolites in patients with PAH. We performed 16S ribosomal RNA gene and shotgun metagenomics sequencing on stool from patients with PAH, family control subjects, and healthy control subjects. We measured markers of inflammation, gut permeability, and microbial metabolites in plasma from patients with PAH, family control subjects, and healthy control subjects. The gut microbiome was less diverse in patients with PAH. Shannon diversity index correlated with measures of pulmonary vascular disease but not with right ventricular function. Patients with PAH had a distinct gut microbial signature at the phylogenetic level, with fewer copies of gut microbial genes that produce antiinflammatory short-chain fatty acids (SCFAs) and secondary bile acids and lower relative abundances of species encoding these genes. Consistent with the gut microbial changes, patients with PAH had relatively lower plasma concentrations of SCFAs and secondary bile acids. Patients with PAH also had enrichment of species with the microbial genes that encoded the proinflammatory microbial metabolite trimethylamine. The changes in the gut microbiome and circulating microbial metabolites between patients with PAH and family control subjects were not as substantial as the differences between patients with PAH and healthy control subjects. Patients with PAH have proinflammatory gut dysbiosis, in which lower circulating SCFAs and secondary bile acids may facilitate pulmonary vascular disease. These findings support investigating modulation of the gut microbiome as a potential treatment for PAH.
10.1164/rccm.202203-0490OC
Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms.
Gut microbes
Long-term sequelae of coronavirus disease (COVID)-19 are frequent and of major concern. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the host gut microbiota, which is linked to disease severity in patients with COVID-19. Here, we report that the gut microbiota of post-COVID subjects had a remarkable predominance of strains with an antibiotic-resistant phenotype compared to healthy controls. Additionally, short-chain fatty acid (SCFA) levels were reduced in feces. Fecal transplantation from post-COVID subjects to germ-free mice led to lung inflammation and worse outcomes during pulmonary infection by multidrug-resistant . transplanted mice also exhibited poor cognitive performance. Overall, we show prolonged impacts of SARS-CoV-2 infection on the gut microbiota that persist after subjects have cleared the virus. Together, these data demonstrate that the gut microbiota can directly contribute to post-COVID sequelae, suggesting that it may be a potential therapeutic target.
10.1080/19490976.2023.2249146
Gut Microbiota and Allergic Disease. New Insights.
Lynch Susan V
Annals of the American Thoracic Society
The rapid rise in childhood allergies (atopy) in Westernized nations has implicated associated environmental exposures and lifestyles as primary drivers of disease development. Culture-based microbiological studies indicate that atopy has demonstrable ties to altered gut microbial colonization in very early life. Infants who exhibit more severe multisensitization to food- or aero-allergens have a significantly higher risk of subsequently developing asthma in childhood. Hence an emerging hypothesis posits that environment- or lifestyle-driven aberrancies in the early-life gut microbiome composition and by extension, microbial function, represent a key mediator of childhood allergic asthma. Animal studies support this hypothesis. Environmental microbial exposures epidemiologically associated with allergy protection in humans confer protection against airway allergy in mice. In addition, gut microbiome-derived short-chain fatty acids produced from a high-fiber diet have been shown to protect against allergy via modulation of both local and remote mucosal immunity as well as hematopoietic antigen-presenting cell populations. Here we review key data supporting the concept of a gut-airway axis and its critical role in childhood atopy.
10.1513/AnnalsATS.201507-451MG
Intestinal Microbiota-derived Propionic Acid Protects against Zinc Oxide Nanoparticle-induced Lung Injury.
American journal of respiratory cell and molecular biology
With the rapid development of nanotechnology, the risks of accidental and/or occupational exposure to zinc oxide nanoparticles (ZnONPs) are increasing. Inhalation of ZnONPs induces metal fume fever in humans and acute lung injury (ALI) in animal models. Although the intestinal microbiota is considered an important modulator of various diseases, the role and mechanism of intestinal microbiota in the pathology of ZnONP-induced ALI are unclear. Herein, we established an intratracheal instillation of a ZnONP-induced ALI mouse model and found that the inhalation of ZnONPs caused ALI along with a perturbation of intestinal flora. Antibiotic cocktail treatment-mediated depletion of intestinal microbiota aggravated ZnONP-induced ALI, and in contrast, fecal microbiota transplantation-mediated restoration of intestinal microbiota exerted the opposite effects. A decrease in short-chain fatty acids, the intestinal microbiota-derived metabolites in the plasma-in particular, acetic acid and propionic acid-occurred after exposure to ZnONPs. It is important to note that supplementation with propionic acid, but not acetic acid, ameliorated ZnONP-induced ALI. We also showed that the source of inflammatory cytokines might partially be the infiltration of macrophages. Supplementation with propionic acid was found to act on macrophages through the receptor GPR43, because knockdown of GPR43 sharply reversed the protective effects of propionic acid during the ZnONP-induced inflammatory response and oxidative stress in both primary alveolar macrophages and RAW 264.7 macrophage cell lines. Altogether, a novel gut-lung axis mechanism is revealed in which intestinal microbiota and their derived metabolite propionic acid play protective roles against ZnONP-induced ALI and suggest that fecal microbiota transplantation and supplementation with propionic acid are potential remedy strategies.
10.1165/rcmb.2021-0515OC
Gut microbiota mediate vascular dysfunction in a murine model of sleep apnoea: effect of probiotics.
The European respiratory journal
BACKGROUND:Obstructive sleep apnoea (OSA) is a chronic prevalent condition characterised by intermittent hypoxia (IH), and is associated with endothelial dysfunction and coronary artery disease (CAD). OSA can induce major changes in gut microbiome diversity and composition, which in turn may induce the emergence of OSA-associated morbidities. However, the causal effects of IH-induced gut microbiome changes on the vasculature remain unexplored. Our objective was to assess if vascular dysfunction induced by IH is mediated through gut microbiome changes. METHODS:Faecal microbiota transplantation (FMT) was conducted on C57BL/6J naïve mice for 6 weeks to receive either IH or room air (RA) faecal slurry with or without probiotics (VSL#3). In addition to 16S rRNA amplicon sequencing of their gut microbiome, FMT recipients underwent arterial blood pressure and coronary artery and aorta function testing, and their trimethylamine -oxide (TMAO) and plasma acetate levels were determined. Finally, C57BL/6J mice were exposed to IH, IH treated with VSL#3 or RA for 6 weeks, and arterial blood pressure and coronary artery function assessed. RESULTS:Gut microbiome taxonomic profiles correctly segregated IH from RA in FMT mice and the normalising effect of probiotics emerged. Furthermore, IH-FMT mice exhibited increased arterial blood pressure and TMAO levels, and impairments in aortic and coronary artery function (p<0.05) that were abrogated by probiotic administration. Lastly, treatment with VSL#3 under IH conditions did not attenuate elevations in arterial blood pressure or CAD. CONCLUSIONS:Gut microbiome alterations induced by chronic IH underlie, at least partially, the typical cardiovascular disturbances of sleep apnoea and can be mitigated by concurrent administration of probiotics.
10.1183/13993003.00002-2022
Effects of Fish n-3 PUFAs on Intestinal Microbiota and Immune System.
Marine drugs
Studies over several decades have documented the beneficial actions of n-3 polyunsaturated fatty acids (PUFAs), which are plentiful in fish oil, in different disease states. Mechanisms responsible for the efficacy of n-3 PUFAs include: (1) Reduction of triglyceride levels; (2) anti-arrhythmic and antithrombotic effects, and (3) resolution of inflammatory processes. The human microbiota project and subsequent studies using next-generation sequencing technology have highlighted that thousands of different microbial species are present in the human gut, and that there has been a significant variability of taxa in the microbiota composition among people. Several factors (gestational age, mode of delivery, diet, sanitation and antibiotic treatment) influence the bacterial community in the human gastrointestinal tract, and among these diet habits play a crucial role. The disturbances in the gut microbiota composition, i.e., gut dysbiosis, have been associated with diseases ranging from localized gastrointestinal disorders to neurologic, respiratory, metabolic, ocular, and cardiovascular illnesses. Many studies have been published about the effects of probiotics and prebiotics on the gut microbiota/microbioma. On the contrary, PUFAs in the gut microbiota have been less well defined. However, experimental studies suggested that gut microbiota, n-3 PUFAs, and host immune cells work together to ensure the intestinal wall integrity. This review discussed current evidence concerning the links among gut microbiota, n-3 PUFAs intake, and human inflammatory disease.
10.3390/md17060374
Delayed gut microbiota maturation in the first year of life is a hallmark of pediatric allergic disease.
Nature communications
Allergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e., the microorganisms and their genes within the gastrointestinal tract. Maturation of the infant immune system and gut microbiota occur in parallel; thus, the conformation of the microbiome may determine if tolerant immune programming arises within the infant. Here we show, using deeply phenotyped participants in the CHILD birth cohort (n = 1115), that there are early-life influences and microbiome features which are uniformly associated with four distinct allergic diagnoses at 5 years: atopic dermatitis (AD, n = 367), asthma (As, n = 165), food allergy (FA, n = 136), and allergic rhinitis (AR, n = 187). In a subset with shotgun metagenomic and metabolomic profiling (n = 589), we discover that impaired 1-year microbiota maturation may be universal to pediatric allergies (AD p = 0.000014; As p = 0.0073; FA p = 0.00083; and AR p = 0.0021). Extending this, we find a core set of functional and metabolic imbalances characterized by compromised mucous integrity, elevated oxidative activity, decreased secondary fermentation, and elevated trace amines, to be a significant mediator between microbiota maturation at age 1 year and allergic diagnoses at age 5 years (β = -2.28; p = 0.0020). Microbiota maturation thus provides a focal point to identify deviations from normative development to predict and prevent allergic disease.
10.1038/s41467-023-40336-4
The lung, the niche, and the microbe: Exploring the lung microbiome in cancer and immunity.
Frontiers in immunology
The lung is a complex and unique organ system whose biology is strongly influenced by environmental exposure, oxygen abundance, connection to extrapulmonary systems a dense capillary network, and an array of immune cells that reside in the tissue at steady state. The lung also harbors a low biomass community of commensal microorganisms that are dynamic during both health and disease with the capacity to modulate regulatory immune responses during diseases such as cancer. Lung cancer is the third most common cancer worldwide with the highest mortality rate amongst cancers due to the difficulty of an early diagnosis. This review discusses the current body of work addressing the interactions between the lung microbiota and the immune system, and how these two components of the pulmonary system are linked to lung cancer development and outcomes. Bringing in lessons from broader studies examining the effects of the gut microbiota on cancer outcomes, we highlight many challenges and gaps in this nascent field.
10.3389/fimmu.2022.1094110
Alterations in human intestinal microbiota in the course of SARS-CoV-2 virus infection.
Przeglad epidemiologiczny
There is an interaction between the bacteria and the host at the genetic, metabolic and immunological levels. The intestine is the largest immune organ in the human's body, and the microbes present in it influence the immune response. An imbalance in the type and the number of bacteria can affect human health. The study attempts to review the current reports on intestinal dysbiosis in the course of SARS-CoV-2 infection and the impact of the composition of the intestinal microbiome on the course and severity of COVID-19 disease.
10.32394/pe.76.15
How to adapt an intestinal microbiota transplantation programme to reduce the risk of invasive multidrug-resistant infection.
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
BACKGROUND:Vulnerable patients with intestinal colonization of multidrug-resistant organisms (MDROs) are recognized to be at increased risk of invasive MDRO-driven infection. Intestinal microbiota transplantation (IMT, also called faecal microbiota transplant) is the transfer of healthy screened donor stool to an affected recipient, and recent interest has focused on its impact on the reduction of invasive MDRO infection. OBJECTIVES:To describe how to establish a clinical IMT pathway for patients at risk of MDRO invasive infection, with special considerations for optimizing administration and assessment of endpoints. SOURCES:Expert guidelines and peer-reviewed clinical studies are encompassed and discussed. CONTENT:IMT is offered to patients with MDROs detected on rectal or stool screening and either at risk of MDRO invasive infection due to altered immune status or those with recurrent MDRO-mediated invasive disease and considered at risk of further disease. Donor screening should include pathogens with theoretical or demonstrated risk of transmission (including MDROs themselves and SARS-CoV-2) and take into consideration the relative immunosuppressed state of potential recipients. Delivery of IMT is timed for when the patient is free from active infection, but no additional antibiotics are indicated. If administered when future immunosuppression is to take place, IMT is aligned at least 2 weeks beforehand to ensure sufficient time for engraftment. Patients are followed up in terms of adverse effects from IMT and clinicians are advised to discuss with the IMT multidisciplinary team on choice of antibiotics if needed to take into consideration the impact upon the intestinal microbiome. Prevention of invasive disease is the primary measure of success, rather than using intestinal decolonization as a binary outcome. Repeat IMT is considered case by case. IMPLICATIONS:Future research areas should include randomized studies that consider clinical outcomes and cost-effectiveness, and better understanding of mechanisms to identify markers of treatment success and functional microbiome components that could be used therapeutically.
10.1016/j.cmi.2021.11.006
Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome.
Gut
BACKGROUND:Long-term complications after COVID-19 are common, but the potential cause for persistent symptoms after viral clearance remains unclear. OBJECTIVE:To investigate whether gut microbiome composition is linked to post-acute COVID-19 syndrome (PACS), defined as at least one persistent symptom 4 weeks after clearance of the SARS-CoV-2 virus. METHODS:We conducted a prospective study of 106 patients with a spectrum of COVID-19 severity followed up from admission to 6 months and 68 non-COVID-19 controls. We analysed serial faecal microbiome of 258 samples using shotgun metagenomic sequencing, and correlated the results with persistent symptoms at 6 months. RESULTS:At 6 months, 76% of patients had PACS and the most common symptoms were fatigue, poor memory and hair loss. Gut microbiota composition at admission was associated with occurrence of PACS. Patients without PACS showed recovered gut microbiome profile at 6 months comparable to that of non-COVID-19 controls. Gut microbiome of patients with PACS were characterised by higher levels of , and lower levels of . Persistent respiratory symptoms were correlated with opportunistic gut pathogens, and neuropsychiatric symptoms and fatigue were correlated with nosocomial gut pathogens, including and (all p<0.05). Butyrate-producing bacteria, including and showed the largest inverse correlations with PACS at 6 months. CONCLUSION:These findings provided observational evidence of compositional alterations of gut microbiome in patients with long-term complications of COVID-19. Further studies should investigate whether microbiota modulation can facilitate timely recovery from post-acute COVID-19 syndrome.
10.1136/gutjnl-2021-325989
Evaluation of Intestinal Microbiota in Children With Sickle Cell Disease.
Journal of pediatric hematology/oncology
BACKGROUND AND AIMS:Sickle cell disease (SCD) is a chronic hemolytic anemia that may be life-threatening due to multisystemic effects. Identification of the factors which affect the pathophysiology of the disease is important in reducing mortality and morbidity. This study aimed to determine gut microbial diversity in children and adolescents with SCA compared with healthy volunteers and to evaluate the clinical impact of microbiota. MATERIALS AND METHODS:The study included 34 children and young adolescents with SCD and 41 healthy volunteer participants. The microbiome was assessed by 16S rRNA sequencing in stool samples. Laboratory parameters of all participants, such as complete blood count and C-reactive protein values and clinical characteristics of SCD patients, were determined and compared, as well as clinical conditions of the patients, such as vascular occlusive crisis and/or acute chest syndrome, frequency of transfusions, intake of penicillin, hydroxyurea, and chelation therapy were recorded. RESULTS:White blood cell count, hemoglobin, immature granulocyte and C-reactive protein levels were significantly higher in the patient group ( P <0.05). Microbiota analysis revealed 3 different clusters among subjects; controls and 2 clusters in the SCD patients (patient G1 and G2 groups). Bacteroides spp. were more prevalent, while Dialester spp. and Prevotella spp. were less prevalent in SCD compared with controls ( t =2.142, P <0.05). Patient G2 (n=9) had a higher prevalence of Bacteroides and a lower prevalence of Prevotella than patient G1 (n=25). CONCLUSION:In our study, there was a difference between SCD patients and the control group, while 2 different microbiota profiles were encountered in SCD patients. This difference between the microbiota of the patients was not found to affect the clinical picture (such as vascular occlusive crisis, acute chest syndrome).
10.1097/MPH.0000000000002725
Intestinal microbiota composition of children with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome (MIS-C).
European journal of pediatrics
Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19. There are studies evaluating the microbiota composition at the time of diagnosis and during the course of COVID-19, especially in adults, while studies in children are limited and no study available in children with multisystem inflammatory syndrome in children (MIS-C). This study was planned to compare intestinal microbiota composition in children diagnosed with MIS-C and acute COVID-19 infection with healthy children. In this prospective multicenter study, 25 children diagnosed with MIS-C, 20 with COVID-19 infection, and 19 healthy children were included. Intestinal microbiota composition was evaluated by 16 s rRNA gene sequencing. We observed changes of diversity, richness, and composition of intestinal microbiota in MIS-C cases compared to COVID-19 cases and in the healthy controls. The Shannon index was higher in the MIS-C group than the healthy controls (p < 0.01). At phylum level, in the MIS-C group, a significantly higher relative abundance of Bacteroidetes and lower abundance of Firmicutes was found compared to the control group. Intestinal microbiota composition changed in MIS-C cases compared to COVID-19 and healthy controls, and Faecalibacterium prausnitzii decreased; Bacteroides uniformis, Bacteroides plebeius, Clostridium ramosum, Eubacterium dolichum, Eggerthella lenta, Bacillus thermoamylovorans, Prevotella tannerae, and Bacteroides coprophilus were dominant in children with MIS-C. At species level, we observed decreased Faecalibacterium prausnitzii, and increased Eubacterium dolichum, Eggerthella lenta, and Bacillus thermoamylovorans in children with MIS-C and increased Bifidobacterium adolescentis and Dorea formicigenerasus in the COVID-19 group. Our study is the first to evaluate the microbiota composition in MIS-C cases. There is a substantial change in the composition of the gut microbiota: (1) reduction of F. prausnitzii in children with MIS-C and COVID-19; (2) an increase of Eggerthella lenta which is related with autoimmunity; and (3) the predominance of E. dolichum is associated with metabolic dysfunctions and obesity in children with MIS-C. CONCLUSIONS: Alterations of the intestinal microbiota might be part of pathogenesis of predisposing factor for MIS-C. It would be beneficial to conduct more extensive studies on the cause-effect relationship of these changes in microbiota composition and their effects on long-term prognosis. WHAT IS KNOWN:• Microbiota composition may play a role in the development, prognosis, or post-infection of COVID-19. • However, the number of studies on children is limited, and no study on multisystem inflammatory syndrome in children is currently available (MIS-C). WHAT IS NEW:• In individuals with MIS-C, the composition of the gut microbiota changed dramatically. • Decreased Faecalibacterium prausnitzii have been observed, increased Eggerthella lenta, which was previously linked to autoimmunity, and predominance of Eubacterium dolichum which was linked to metabolic dysfunction and obesity.
10.1007/s00431-022-04494-9
Associations of Dietary Intake with the Intestinal Microbiota and Short-Chain Fatty Acids Among Young Adults with Type 1 Diabetes and Overweight or Obesity.
The Journal of nutrition
BACKGROUND:Diet, a key component of type 1 diabetes (T1D) management, modulates the intestinal microbiota and its metabolically active byproducts-including SCFA-through fermentation of dietary carbohydrates such as fiber. However, the diet-microbiome relationship remains largely unexplored in longstanding T1D. OBJECTIVES:We evaluated whether increased carbohydrate intake, including fiber, is associated with increased SCFA-producing gut microbes, SCFA, and intestinal microbial diversity among young adults with longstanding T1D and overweight or obesity. METHODS:Young adult men and women with T1D for ≥1 y, aged 19-30 y, and BMI of 27.0-39.9 kg/m at baseline provided stool samples at baseline and 3, 6, and 9 mo of a randomized dietary weight loss trial. Diet was assessed by 1-2 24-h recalls. The abundance of SCFA-producing microbes was measured using 16S rRNA gene sequencing. GC-MS measured fecal SCFA (acetate, butyrate, propionate, and total) concentrations. Adjusted and Bonferroni-corrected generalized estimating equations modeled associations of dietary fiber (total, soluble, and pectins) and carbohydrate (available carbohydrate, and fructose) with microbiome-related outcomes. Primary analyses were restricted to data collected before COVID-19 interruptions. RESULTS:Fiber (total and soluble) and carbohydrates (available and fructose) were positively associated with total SCFA and acetate concentrations (n = 40 participants, 52 visits). Each 10 g/d of total and soluble fiber intake was associated with an additional 8.8 μmol/g (95% CI: 4.5, 12.8 μmol/g; P = 0.006) and 24.0 μmol/g (95% CI: 12.9, 35.1 μmol/g; P = 0.003) of fecal acetate, respectively. Available carbohydrate intake was positively associated with SCFA producers Roseburia and Ruminococcus gnavus. All diet variables except pectin were inversely associated with normalized abundance of Bacteroides and Alistipes. Fructose was inversely associated with Akkermansia abundance. CONCLUSIONS:In young adults with longstanding T1D, fiber and carbohydrate intake were associated positively with fecal SCFA but had variable associations with SCFA-producing gut microbes. Controlled feeding studies should determine whether gut microbes and SCFA can be directly manipulated in T1D.
10.1016/j.tjnut.2022.12.017
Early-Life Lung and Gut Microbiota Development and Respiratory Syncytial Virus Infection.
Frontiers in immunology
Several environmental factors can influence the development and establishment of the early-life microbiota. For example, exposure to different environmental factors from birth to childhood will shape the lung and gut microbiota and the development of the immune system, which will impact respiratory tract infection and widespread disease occurrence during infancy and later in life. Respiratory syncytial virus (RSV) infects most infants by the age of two and is the primary cause of bronchiolitis in children worldwide. Approximately a third of infants hospitalized with bronchiolitis develop asthma later in life. However, it is unclear what factors increase susceptibility to severe RSV-bronchiolitis and the subsequent asthma development. In recent years, the role of the gut and lung microbiota in airway diseases has received increased interest, and more studies have focused on this field. Different epidemiological studies and experimental animal models have associated early-life gut microbiota dysbiosis with an increased risk of lung disease later in life. This work will review published evidence that correlated environmental factors that affect the early-life microbiota composition and their role in developing severe RSV infection.
10.3389/fimmu.2022.877771
Diet and the gut-lung axis in cystic fibrosis - direct & indirect links.
Gut microbes
Cystic fibrosis (CF) is a multisystem, autosomal, recessive disease primarily affecting the lungs, pancreas, gastrointestinal tract, and liver. Whilst there is increasing evidence of a microbial 'gut-lung axis' in chronic respiratory conditions, there has been limited analysis of such a concept in CF. We performed a comprehensive dietary and microbiota analysis to explore the interactions between diet, gastrointestinal microbiota, respiratory microbiota, and clinical outcomes in children with CF. Our results demonstrate significant alterations in intestinal inflammation and respiratory and gastrointestinal microbiota when compared to age and gender matched children without CF. We identified correlations between the gastrointestinal and respiratory microbiota, lung function, CF pulmonary exacerbations and anthropometrics, supporting the concept of an altered gut-lung axis in children with CF. We also identified significant differences in dietary quality with CF children consuming greater relative proportions of total, saturated and trans fats, and less relative proportions of carbohydrates, wholegrains, fiber, insoluble fiber, starch, and resistant starch. Our findings position the CF diet as a potential modulator in gastrointestinal inflammation and the proposed gut-lung axial relationship in CF. The dietary intake of wholegrains, fiber and resistant starch may be protective against intestinal inflammation and should be explored as potential therapeutic adjuvants for children with CF.
10.1080/19490976.2022.2156254
Intestinal Microbiota in the SARS-CoV-2 Infection: What Is Known?
Rodrigues Patrícia Brito,Dos Santos Pereira Gomes Arilson Bernardo,Genaro Lívia Moreira,Pascoal Lívia Bitencourt,de Souza Ana Paula Duarte,Leal Raquel Franco,Vinolo Marco Aurélio Ramirez
Advances in experimental medicine and biology
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, emerged last year in China and quickly spread to millions of people around the world. This virus infects cells in different tissues and causes pulmonary (e.g., pneumonia and acute respiratory distress syndrome), neurological, cardiovascular, and intestinal manifestations, which can be the result of a direct viral effect or secondary to endothelial, thrombotic, or immunological alterations. In this chapter, we discuss recent studies which highlighted the relevance of the intestinal microbiota for other infectious respiratory diseases. We present the "altered microbiota" (dysbiotic) as a point of connection between conditions that are risk factors for the development of severe forms of COVID-19. In addition, we describe the findings of recent studies reporting alterations of microbiota composition in COVID-19 patients and speculate on how this may impact in development of the disease.
10.1007/978-3-030-71697-4_7
Microbiomes in respiratory health and disease: An Asia-Pacific perspective.
Chotirmall Sanjay H,Gellatly Shaan L,Budden Kurtis F,Mac Aogain Micheál,Shukla Shakti D,Wood David L A,Hugenholtz Philip,Pethe Kevin,Hansbro Philip M
Respirology (Carlton, Vic.)
There is currently enormous interest in studying the role of the microbiome in health and disease. Microbiome's role is increasingly being applied to respiratory diseases, in particular COPD, asthma, cystic fibrosis and bronchiectasis. The changes in respiratory microbiomes that occur in these diseases and how they are modified by environmental challenges such as cigarette smoke, air pollution and infection are being elucidated. There is also emerging evidence that gut microbiomes play a role in lung diseases through the modulation of systemic immune responses and can be modified by diet and antibiotic treatment. There are issues that are particular to the Asia-Pacific region involving diet and prevalence of specific respiratory diseases. Each of these issues is further complicated by the effects of ageing. The challenges now are to elucidate the cause and effect relationships between changes in microbiomes and respiratory diseases and how to translate these into new treatments and clinical care. Here we review the current understanding and progression in these areas.
10.1111/resp.12971
Gut microbiota in COVID-19: new insights from inside.
Gut microbes
The epidemic of coronavirus disease-19 (COVID-19) has grown to be a global health threat. Gastrointestinal symptoms are thought to be common clinical manifestations apart from a series of originally found respiratory symptoms. The human gut harbors trillions of microorganisms that are indispensable for complex physiological processes and homeostasis. Growing evidence demonstrate that gut microbiota alteration is associated with COVID-19 progress and severity, and post-COVID-19 syndrome, characterized by decrease of anti-inflammatory bacteria like and and enrichment of inflammation-associated microbiota including and . Therapeutic strategies such as diet, probiotics/prebiotics, herb, and fecal microbiota transplantation have shown positive effects on relieving clinical symptoms. In this article, we provide and summarize the recent evidence about the gut microbiota and their metabolites alterations during and after COVID-19 infection and focus on potential therapeutic strategies targeting gut microbiota. Understanding the connections between intestinal microbiota and COVID-19 would provide new insights into COVID-19 management in the future.
10.1080/19490976.2023.2201157
Gut Microbiota: the Emerging Link to Lung Homeostasis and Disease.
Journal of bacteriology
The gut microbiota plays a crucial role in the development of the immune system and confers benefits or disease susceptibility to the host. Emerging studies have indicated the gut microbiota could affect pulmonary health and disease through cross talk between the gut microbiota and the lungs. Gut microbiota dysbiosis could lead to acute or chronic lung disease, such as asthma, tuberculosis, and lung cancer. In addition, the composition of the gut microbiota may be associated with different lung diseases, the prevalence of which also varies by age. Modulation of the gut microbiota through short-chain fatty acids, probiotics, and micronutrients may present potential therapeutic strategies to protect against lung diseases. In this review, we will provide an overview of the cross-talk between the gut microbiota and the lungs, as well as elucidate the underlying pathogenesis and/or potential therapeutic strategies of some lung diseases from the point of view of the gut microbiota.
10.1128/JB.00454-20
Intestinal microbiota dysbiosis in children with recurrent respiratory tract infections.
Li Lei,Wang Fang,Liu Yanni,Gu Feng
Microbial pathogenesis
BACKGROUND:The impact of the gut microbiota on recurrent respiratory tract infection (RRTI) remains to be fully elucidated. METHODS:To characterize the gut microbiota in patients with RRTI, fecal samples from 26 patients with RRTI and 23 healthy volunteers were profiled using the Illumina MiSeq platform. Beta diversity (Principal Component Analysis (PCA), Principal Co-ordinates Analysis (PCoA), Non-metric multidimensional scaling (NMDS)) analysis showed that the bacterial community structure segregated differently between the RRTI and control groups. RESULTS:Results from alpha diversity analysis revealed lower microbiota diversity in samples from RRTI patients than in normal controls. Taxonomic analysis illustrated that the abundance of six phyla (Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, Verrucomicrobia, Tenericutes) and four genera (Enterococcus, Faecalibacterium, Bifidobacterium, Eubacterium were significantly different between these two groups. In addition, Enterococcus (P < 0.001) was more enriched in the RRTI group, whereas the abundances of Eubacterium (P < 0.001), Faecalibacterium (0.01 < P < 0.05) and Bifidobacterium (0.01 < P < 0.05) were reduced in the RRTI group compared to those in the normal control group. The performance of the model was assessed using ROC analysis, and Enterococcus, Eubacterium and Bifidobacterium achieved AUC values of 0.860, 0.820, and 0.689, respectively. CONCLUSIONS:These results provide fundamental evidence in support of intestinal microbiota dysbiosis in children with RRTI.
10.1016/j.micpath.2019.103709
Immunoregulatory Intestinal Microbiota and COVID-19 in Patients with Type Two Diabetes: A Double-Edged Sword.
Viruses
Coronavirus disease 2019, or COVID-19, is a major challenge facing scientists worldwide. Alongside the lungs, the system of organs comprising the GI tract is commonly targeted by COVID-19. The dysbiotic modulations in the intestine influence the disease severity, potentially due to the ability of the intestinal microbiota to modulate T lymphocyte functions, i.e., to suppress or activate T cell subpopulations. The interplay between the lungs and intestinal microbiota is named the gut-lung axis. One of the most usual comorbidities in COVID-19 patients is type 2 diabetes, which induces changes in intestinal microbiota, resulting in a pro-inflammatory immune response, and consequently, a more severe course of COVID-19. However, changes in the microbiota in this comorbid pathology remain unclear. Metformin is used as a medication to treat type 2 diabetes. The use of the type 2 diabetes drug metformin is a promising treatment for this comorbidity because, in addition to its hypoglycemic action, it can increase amount of intestinal bacteria that induce regulatory T cell response. This dual activity of metformin can reduce lung damage and improve the course of the COVID-19 disease.
10.3390/v14030477
The gut-lung axis in severe acute Pancreatitis-associated lung injury: The protection by the gut microbiota through short-chain fatty acids.
Pharmacological research
The role of gut microbiota in regulating the intestinal homeostasis, as well as the pathogenesis of severe acute pancreatitis-associated lung injury (PALI) is widely recognized. The bioactive functions of metabolites with small molecule weight and the detail molecular mechanisms of PALI mediated by "gut-lung axis" have gradually raised the attentions of researchers. Several studies have proved that short-chain fatty acids (SCFAs) produced by gut microbiome play crucial roles and varied activities in the process of PALI. However, relevant reviews reporting SCFAs in the involvement of PALI is lacking. In this review, we firstly introduced the synthetic and metabolic pathways of SCFAs, as well as the transport and signal transduction routes in brief. Afterwards, we focused on the possible mechanisms and clues of SCFAs to participate in the fight against PALI which referred to the inhibition of pathogen proliferation, anti-inflammatory effects, enhancement of intestinal barrier functions, and the maintenance and regulation of immune homeostasis via pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). In addition, the latest reported pathological and physiological mechanisms of the gut-lung axis involved in PALI were reviewed. Finally, we summarized the potential therapeutic interventions of PALI by targeting SCFAs, including dietary fiber supplementation, direct supplementation of SCFAs/prebiotics/probiotics, and drugs administration, which is expected to provide new sights for clinical use in the future.
10.1016/j.phrs.2022.106321
Review article: how the intestinal microbiota may reflect disease activity and influence therapeutic outcome in inflammatory bowel disease.
Caenepeel Clara,Sadat Seyed Tabib Nasim,Vieira-Silva Sara,Vermeire Séverine
Alimentary pharmacology & therapeutics
BACKGROUND:Intestinal bacteria produce metabolites and by-products necessary for homeostasis. Imbalance in this equilibrium is linked to multiple pathologies including inflammatory bowel disease (IBD). The role of the gut microbiota in determining treatment response is becoming apparent, and may act as biomarker for efficacy. AIM:To describe knowledge about the intestinal microbiota on disease severity and treatment outcomes in IBD METHODS: Descriptive review using PubMed to identify literature on the intestinal microbiota in IBD RESULTS: Severe IBD has a less diverse microbiota with fewer commensal microbiota communities and more opportunistic pathogenic bacteria originating from the oral cavity or respiratory tract. IBD treatments can alter gut microbiota composition, but in vitro/in vivo studies are needed to prove causation. A diversification of the microbiota is observed during remission. Patients with a more diverse baseline microbiome and higher microbial diversity show better response to anti-tumour necrosis factor-α, vedolizumab and ustekinumab therapy. Higher abundance of short chain fatty acid-producing bacteria, fewer mucus-colonising bacteria and lower abundance of pro-inflammatory bacteria have also been associated with a favourable outcome. Predictive models, based on a combination of microbiota, clinical data and serological markers, have good accuracy for treatment outcome and disease severity. CONCLUSION:The intestinal microbiota in IBD carries a set of promising biomarkers of disease activity and prediction of therapeutic outcome. Current insights may also help in designing microbiota modulation strategies to improve outcomes in IBD.
10.1111/apt.16096
The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia.
Schuijt Tim J,Lankelma Jacqueline M,Scicluna Brendon P,de Sousa e Melo Felipe,Roelofs Joris J T H,de Boer J Daan,Hoogendijk Arjan J,de Beer Regina,de Vos Alex,Belzer Clara,de Vos Willem M,van der Poll Tom,Wiersinga W Joost
Gut
OBJECTIVE:Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections. DESIGN:We depleted the gut microbiota in C57BL/6 mice and subsequently infected them intranasally with S. pneumoniae. We then performed survival and faecal microbiota transplantation (FMT) experiments and measured parameters of inflammation and alveolar macrophage whole-genome responses. RESULTS:We found that the gut microbiota protects the host during pneumococcal pneumonia, as reflected by increased bacterial dissemination, inflammation, organ damage and mortality in microbiota-depleted mice compared with controls. FMT in gut microbiota-depleted mice led to a normalisation of pulmonary bacterial counts and tumour necrosis factor-α and interleukin-10 levels 6 h after pneumococcal infection. Whole-genome mapping of alveolar macrophages showed upregulation of metabolic pathways in the absence of a healthy gut microbiota. This upregulation correlated with an altered cellular responsiveness, reflected by a reduced responsiveness to lipopolysaccharide and lipoteichoic acid. Compared with controls, alveolar macrophages derived from gut microbiota-depleted mice showed a diminished capacity to phagocytose S. pneumoniae. CONCLUSIONS:This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut-lung axis in bacterial infections.
10.1136/gutjnl-2015-309728
The Crosstalk between the Gut Microbiota Composition and the Clinical Course of Allergic Rhinitis: The Use of Probiotics, Prebiotics and Bacterial Lysates in the Treatment of Allergic Rhinitis.
Nutrients
Although massive progress in discovering allergic rhinitis (AR) aetiology has been made in recent years, its prevalence is still rising and it significantly impacts patients' lives. That is why further and non-conventional research elucidating the role of new factors in AR pathogenesis is needed, facilitating discoveries of new treatment approaches. One of these factors is the gut microbiota, with its specific roles in health and disease. This review presents the process of gut microbiota development, especially in early life, focusing on its impact on the immune system. It emphasizes the link between the gut microbiota composition and immune changes involved in AR development. Specifically, it elucidates the significant link between bacteria colonizing the gut and the Th1/Th2 imbalance. Probiotics, prebiotics and bacterial lysates, which are medications that restore the composition of intestinal bacteria and indirectly affect the clinical course of AR, are also discussed.
10.3390/nu14204328
Probiotics and Covid-19.
Bottari Benedetta,Castellone Vincenzo,Neviani Erasmo
International journal of food sciences and nutrition
Coronavirus disease 2019 (COVID-19) has become pandemic very rapidly at the beginning of 2020. In the rush to possible therapeutic options, probiotics administration has been proposed mainly based on indirect observation. Some evidence of COVID-19 effects on intestinal microbiota dysbiosis has been shown and probiotics have been considered for their efficacy in the management of respiratory tract viral infections. These observations could be reinforced by the more and more evident existence of a lung-gut axis, suggesting the modulation of gut microbiota among the approaches to the COVID-19 prevention and treatment. As different possible roles of probiotics in this extremely severe illness have been contemplated, the aim of this work is to collect all the currently available information related to this topic, providing a starting point for future studies focussing on it.
10.1080/09637486.2020.1807475
The gut microbiome is a significant risk factor for future chronic lung disease.
The Journal of allergy and clinical immunology
BACKGROUND:The gut-lung axis is generally recognized, but there are few large studies of the gut microbiome and incident respiratory disease in adults. OBJECTIVE:We sought to investigate the association and predictive capacity of the gut microbiome for incident asthma and chronic obstructive pulmonary disease (COPD). METHODS:Shallow metagenomic sequencing was performed for stool samples from a prospective, population-based cohort (FINRISK02; N = 7115 adults) with linked national administrative health register-derived classifications for incident asthma and COPD up to 15 years after baseline. Generalized linear models and Cox regressions were used to assess associations of microbial taxa and diversity with disease occurrence. Predictive models were constructed using machine learning with extreme gradient boosting. Models considered taxa abundances individually and in combination with other risk factors, including sex, age, body mass index, and smoking status. RESULTS:A total of 695 and 392 statistically significant associations were found between baseline taxonomic groups and incident asthma and COPD, respectively. Gradient boosting decision trees of baseline gut microbiome abundance predicted incident asthma and COPD in the validation data sets with mean area under the curves of 0.608 and 0.780, respectively. Cox analysis showed that the baseline gut microbiome achieved higher predictive performance than individual conventional risk factors, with C-indices of 0.623 for asthma and 0.817 for COPD. The integration of the gut microbiome and conventional risk factors further improved prediction capacities. CONCLUSIONS:The gut microbiome is a significant risk factor for incident asthma and incident COPD and is largely independent of conventional risk factors.
10.1016/j.jaci.2022.12.810
Coronavirus disease-2019 and the intestinal tract: An overview.
World journal of gastroenterology
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can progress to a severe respiratory and systemic disease named coronavirus disease-2019 (COVID-19). The most common symptoms are fever and respiratory discomfort. Nevertheless, gastrointestinal infections have been reported, with symptoms such as diarrhea, nausea, vomiting, abdominal pain, and lack of appetite. Importantly, SARS-CoV-2 can remain positive in fecal samples after nasopharyngeal clearance. After gastrointestinal SARS-CoV-2 infection and other viral gastrointestinal infections, some patients may develop alterations in the gastrointestinal microbiota. In addition, some COVID-19 patients may receive antibiotics, which may also disturb gastrointestinal homeostasis. In summary, the gastrointestinal system, gut microbiome, and gut-lung axis may represent an important role in the development, severity, and treatment of COVID-19. Therefore, in this review, we explore the current pieces of evidence of COVID-19 gastrointestinal manifestations, possible implications, and interventions.
10.3748/wjg.v27.i13.1255
Unraveling the Mystery Surrounding Post-Acute Sequelae of COVID-19.
Ramakrishnan Rakhee K,Kashour Tarek,Hamid Qutayba,Halwani Rabih,Tleyjeh Imad M
Frontiers in immunology
More than one year since its emergence, corona virus disease 2019 (COVID-19) is still looming large with a paucity of treatment options. To add to this burden, a sizeable subset of patients who have recovered from acute COVID-19 infection have reported lingering symptoms, leading to significant disability and impairment of their daily life activities. These patients are considered to suffer from what has been termed as "chronic" or "long" COVID-19 or a form of post-acute sequelae of COVID-19, and patients experiencing this syndrome have been termed COVID-19 long-haulers. Despite recovery from infection, the persistence of atypical chronic symptoms, including extreme fatigue, shortness of breath, joint pains, brain fogs, anxiety and depression, that could last for months implies an underlying disease pathology that persist beyond the acute presentation of the disease. As opposed to the direct effects of the virus itself, the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be largely responsible for the appearance of these lasting symptoms, possibly through facilitating an ongoing inflammatory process. In this review, we hypothesize potential immunological mechanisms underlying these persistent and prolonged effects, and describe the multi-organ long-term manifestations of COVID-19.
10.3389/fimmu.2021.686029
The role of microbiota in respiratory health and diseases, particularly in tuberculosis.
Shah Taif,Shah Zahir,Baloch Zulqarnain,Cui XiuMing
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Trillions of beneficial and hostile microorganisms live in the human respiratory and gastrointestinal tracts, which act as gatekeepers in maintaining human health, i.e., protecting the body from pathogens by colonizing mucosal surfaces with microbiota-derived antimicrobial metabolites such as short-chain fatty acids or host-derived cytokines and chemokines. It is widely accepted that the microbiome interacts with each other and with the host in a mutually beneficial relationship. Microbiota in the respiratory tract may also play a crucial role in immune homeostasis, maturation, and maintenance of respiratory physiology. Anti-TB antibiotics may cause dysbiosis in the lung and intestinal microbiota, affecting colonization resistance and making the host more susceptible to Mycobacterium tuberculosis (M. tuberculosis) infection. This review discusses recent advances in our understanding of the lung microbiota composition, the lungs and intestinal microbiota related to respiratory health and diseases, microbiome sequencing and analysis, the bloodstream, and the lymphatic system that underpin the gut-lung axis in M. tuberculosis-infected humans and animals. We also discuss the gut-lung axis interactions with the immune system, the role of the microbiome in TB pathogenesis, and the impact of anti-TB antibiotic therapy on the microbiota in animals, humans, and drug-resistant TB individuals.
10.1016/j.biopha.2021.112108
Assessment of microbiota in the gut and upper respiratory tract associated with SARS-CoV-2 infection.
Microbiome
BACKGROUND:The human microbiome plays an important role in modulating the host metabolism and immune system. Connections and interactions have been found between the microbiome of the gut and oral pharynx in the context of SARS-CoV-2 and other viral infections; hence, to broaden our understanding of host-viral responses in general and to deepen our knowledge of COVID-19, we performed a large-scale, systematic evaluation of the effect of SARS-CoV-2 infection on human microbiota in patients with varying disease severity. RESULTS:We processed 521 samples from 203 COVID-19 patients with varying disease severity and 94 samples from 31 healthy donors, consisting of 213 pharyngeal swabs, 250 sputa, and 152 fecal samples, and obtained meta-transcriptomes as well as SARS-CoV-2 sequences from each sample. Detailed assessment of these samples revealed altered microbial composition and function in the upper respiratory tract (URT) and gut of COVID-19 patients, and these changes are significantly associated with disease severity. Moreover, URT and gut microbiota show different patterns of alteration, where gut microbiome seems to be more variable and in direct correlation with viral load; and microbial community in the upper respiratory tract renders a high risk of antibiotic resistance. Longitudinally, the microbial composition remains relatively stable during the study period. CONCLUSIONS:Our study has revealed different trends and the relative sensitivity of microbiome in different body sites to SARS-CoV-2 infection. Furthermore, while the use of antibiotics is often essential for the prevention and treatment of secondary infections, our results indicate a need to evaluate potential antibiotic resistance in the management of COVID-19 patients in the ongoing pandemic. Moreover, a longitudinal follow-up to monitor the restoration of the microbiome could enhance our understanding of the long-term effects of COVID-19. Video Abstract.
10.1186/s40168-022-01447-0
Relationship between Gut Microbiota and Allergies in Children: A Literature Review.
Nutrients
The intestinal microbiota is a diverse and complex microecosystem that lives and thrives within the human body. The microbiota stabilizes by the age of three. This microecosystem plays a crucial role in human health, particularly in the early years of life. Dysbiosis has been linked to the development of various allergic diseases with potential long-term implications. Next-generation sequencing methods have established that allergic diseases are associated with dysbiosis. These methods can help to improve the knowledge of the relationship between dysbiosis and allergic diseases. The aim of this review paper is to synthesize the current understanding on the development of the intestinal microbiota in children, the long-term impact on health, and the relationship between dysbiosis and allergic diseases. Furthermore, we examine the connection between the microbiome and specific allergies such as atopic dermatitis, asthma, and food allergies, and which mechanisms could determine the induction of these diseases. Furthermore, we will review how factors such as mode of delivery, antibiotic use, breastfeeding, and the environment influence the development of the intestinal flora, as well as review various interventions for the prevention and treatment of gut microbiota-related allergies.
10.3390/nu15112529
Causal relationship between Gut Microbiota and Obstructive sleep apnea.
Archives of gerontology and geriatrics
OBJECTIVE:Although observational studies have identified relations between gut microbiota and obstructive sleep apnea (OSA), their causal links remain elusive. Hence, we aimed to investigate this causal relation using the Mendelian randomization (MR) approach. METHODS:Summary-level gut microbiota data were acquired using the maximum available genome-wide association study (GWAS) from the MiBioGen consortium while obtaining summary-level OSA data using publicly available GWAS from the FinnGen Consortium. A two-sample MR analysis was used for assessing gut microbiota and OSA causal effect, using the inverse variance-weighted (IVW) approach as the primary analysis method. The results were further examined for pleiotropy and heterogeneity. Moreover, the reverse MR analysis did not find a causal relationship. RESULTS:Four gut microbiota were found to have nominally significant association to OSA according to the IVW method. Among them, the family Peptostreptococcaceae (OR = 1.171, 95% CI: 1.027-1.334) and genus Coprococcus3 (OR = 1.163, 95% CI: 1.007-1.343), these two florae that may increase the risk of OSA. Family Acidaminococcaceae (OR = 0.843, 95% CI: 0.729-0.975) and genus Blautia (OR = 0.830, 95% CI: 0.708-0.972) may have an ameliorative effect on OSA. No evidence of pleiotropy or heterogeneity was found. CONCLUSIONS:MR analysis indicated that a causal relation is existed between specific gut microbiota and OSA at the genetic prediction level, offering innovative perspectives into the mechanisms underlying gut microbiota-mediated OSA development.
10.1016/j.archger.2023.105052
The microbiome and critical illness.
The Lancet. Respiratory medicine
The central role of the microbiome in critical illness is supported by a half century of experimental and clinical study. The physiological effects of critical illness and the clinical interventions of intensive care substantially alter the microbiome. In turn, the microbiome predicts patients' susceptibility to disease, and manipulation of the microbiome has prevented or modulated critical illness in animal models and clinical trials. This Review surveys the microbial ecology of critically ill patients, presents the facts and unanswered questions surrounding gut-derived sepsis, and explores the radically altered ecosystem of the injured alveolus. The revolution in culture-independent microbiology has provided the tools needed to target the microbiome rationally for the prevention and treatment of critical illness, holding great promise to improve the acute and chronic outcomes of the critically ill.
10.1016/S2213-2600(15)00427-0
Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization.
Gastroenterology
BACKGROUND & AIMS:Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gastrointestinal tissues, little is known about the roles of gut commensal microbes in susceptibility to and severity of infection. We investigated changes in fecal microbiomes of patients with SARS-CoV-2 infection during hospitalization and associations with severity and fecal shedding of virus. METHODS:We performed shotgun metagenomic sequencing analyses of fecal samples from 15 patients with Coronavirus Disease 2019 (COVID-19) in Hong Kong, from February 5 through March 17, 2020. Fecal samples were collected 2 or 3 times per week from time of hospitalization until discharge; disease was categorized as mild (no radiographic evidence of pneumonia), moderate (pneumonia was present), severe (respiratory rate ≥30/min, or oxygen saturation ≤93% when breathing ambient air), or critical (respiratory failure requiring mechanical ventilation, shock, or organ failure requiring intensive care). We compared microbiome data with those from 6 subjects with community-acquired pneumonia and 15 healthy individuals (controls). We assessed gut microbiome profiles in association with disease severity and changes in fecal shedding of SARS-CoV-2. RESULTS:Patients with COVID-19 had significant alterations in fecal microbiomes compared with controls, characterized by enrichment of opportunistic pathogens and depletion of beneficial commensals, at time of hospitalization and at all timepoints during hospitalization. Depleted symbionts and gut dysbiosis persisted even after clearance of SARS-CoV-2 (determined from throat swabs) and resolution of respiratory symptoms. The baseline abundance of Coprobacillus, Clostridium ramosum, and Clostridium hathewayi correlated with COVID-19 severity; there was an inverse correlation between abundance of Faecalibacterium prausnitzii (an anti-inflammatory bacterium) and disease severity. Over the course of hospitalization, Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis, and Bacteroides ovatus, which downregulate expression of angiotensin-converting enzyme 2 (ACE2) in murine gut, correlated inversely with SARS-CoV-2 load in fecal samples from patients. CONCLUSIONS:In a pilot study of 15 patients with COVID-19, we found persistent alterations in the fecal microbiome during the time of hospitalization, compared with controls. Fecal microbiota alterations were associated with fecal levels of SARS-CoV-2 and COVID-19 severity. Strategies to alter the intestinal microbiota might reduce disease severity.
10.1053/j.gastro.2020.05.048
Imbalance of gut microbiota is involved in the development of chronic obstructive pulmonary disease: A review.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Chronic obstructive pulmonary disease (COPD) is a common chronic disease characterized by chronic airway inflammation and remodeling, which seriously endangers human health. Recent developments in genomics and metabolomics have revealed the roles of the gut microbiota and its metabolites in COPD. Dysbiosis of the gut microbiota directly increases gut permeability, thereby promoting the translocation of pathological bacteria. The gut microbiota and associated metabolites may influence the development and progression of COPD by modulating immunity and inflammation. Furthermore, the systemic hypoxia and oxidative stress that occur in COPD may also be involved in intestinal dysfunction. The cross-talk between the gut and lungs is known as the gut-lung axis; however, an overview of its mechanism is lacking. This review highlights the critical and complex interplay of gut microbiota and immune responses in the gut-lung axis, further explores possible links between the gut and lungs, and summarizes new interventions through diet, probiotics, vitamins, and fecal microbiota transplantation, which are critical to COPD.
10.1016/j.biopha.2023.115150
Viral Infections, the Microbiome, and Probiotics.
Frontiers in cellular and infection microbiology
Viral infections continue to cause considerable morbidity and mortality around the world. Recent rises in these infections are likely due to complex and multifactorial external drivers, including climate change, the increased mobility of people and goods and rapid demographic change to name but a few. In parallel with these external factors, we are gaining a better understanding of the internal factors associated with viral immunity. Increasingly the gastrointestinal (GI) microbiome has been shown to be a significant player in the host immune system, acting as a key regulator of immunity and host defense mechanisms. An increasing body of evidence indicates that disruption of the homeostasis between the GI microbiome and the host immune system can adversely impact viral immunity. This review aims to shed light on our understanding of how host-microbiota interactions shape the immune system, including early life factors, antibiotic exposure, immunosenescence, diet and inflammatory diseases. We also discuss the evidence base for how host commensal organisms and microbiome therapeutics can impact the prevention and/or treatment of viral infections, such as viral gastroenteritis, viral hepatitis, human immunodeficiency virus (HIV), human papilloma virus (HPV), viral upper respiratory tract infections (URTI), influenza and SARS CoV-2. The interplay between the gastrointestinal microbiome, invasive viruses and host physiology is complex and yet to be fully characterized, but increasingly the evidence shows that the microbiome can have an impact on viral disease outcomes. While the current evidence base is informative, further well designed human clinical trials will be needed to fully understand the array of immunological mechanisms underlying this intricate relationship.
10.3389/fcimb.2020.596166
The Gut-Lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks.
Frontiers in cellular and infection microbiology
The gut and lungs are anatomically distinct, but potential anatomic communications and complex pathways involving their respective microbiota have reinforced the existence of a gut-lung axis (GLA). Compared to the better-studied gut microbiota, the lung microbiota, only considered in recent years, represents a more discreet part of the whole microbiota associated to human hosts. While the vast majority of studies focused on the bacterial component of the microbiota in healthy and pathological conditions, recent works have highlighted the contribution of fungal and viral kingdoms at both digestive and respiratory levels. Moreover, growing evidence indicates the key role of inter-kingdom crosstalks in maintaining host homeostasis and in disease evolution. In fact, the recently emerged GLA concept involves host-microbe as well as microbe-microbe interactions, based both on localized and long-reaching effects. GLA can shape immune responses and interfere with the course of respiratory diseases. In this review, we aim to analyze how the lung and gut microbiota influence each other and may impact on respiratory diseases. Due to the limited knowledge on the human virobiota, we focused on gut and lung bacteriobiota and mycobiota, with a specific attention on inter-kingdom microbial crosstalks which are able to shape local or long-reached host responses within the GLA.
10.3389/fcimb.2020.00009
Traditional Chinese medicine against COVID-19: Role of the gut microbiota.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and it has become a public health concern worldwide. In addition to respiratory symptoms, some COVID‑19 patients also show various gastrointestinal symptoms and even consider gastrointestinal symptoms to be the first manifestation. A large amount of evidence has shown that SARS-CoV-2 infection could disrupt the gut microbiota balance, and disorders of the gut microbiota could aggravate the condition of COVID-19 patients. Therefore, maintaining the gut microbiota balance is expected to become a potential new therapeutic target for treating COVID-19. Traditional Chinese medicine (TCM) has significant effects in all stages of the prevention and treatment of COVID-19. It can adjust the gut microbiota and is an ideal intestinal microecological regulator. This review summarizes the advantages and clinical efficacy of TCM in the treatment of COVID-19 and expounds on the relationship between TCM and the gut microbiota, the relationship between COVID-19 and the gut microbiota, the mechanism of gut microbiota disorders induced by SARS-CoV-2, the relationship between cytokine storms and the gut microbiota, and the role and mechanism of TCM in preventing and treating COVID-19 by regulating the gut microbiota to provide new research ideas for TCM in the prevention and treatment of COVID-19.
10.1016/j.biopha.2022.112787
Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory lipopolysaccharide.
Lai Hsin-Chih,Lin Tzu-Lung,Chen Ting-Wen,Kuo Yu-Lun,Chang Chih-Jung,Wu Tsung-Ru,Shu Ching-Chung,Tsai Ying-Huang,Swift Simon,Lu Chia-Chen
Gut
OBJECTIVE:Chronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration. DESIGN:A murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays. RESULTS:Gut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway. CONCLUSION:The gut microbiota-lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.
10.1136/gutjnl-2020-322599
Early Life Microbiota and Respiratory Tract Infections.
de Steenhuijsen Piters Wouter A A,Binkowska Justyna,Bogaert Debby
Cell host & microbe
Over the last decade, it has become clear that respiratory and intestinal tract microbiota are related to pathogenesis of respiratory tract infections (RTIs). Host and environmental factors can drive respiratory microbiota maturation in early life, which in turn is related to consecutive susceptibility to RTIs. Moreover, during RTIs, including viral bronchiolitis, the local microbiome appears to play an immunomodulatory role through complex interactions, though causality has not yet been fully demonstrated. The microbiota is subsequently associated with recovery after RTIs and can be related to persistent or long-term sequelae. In this Review, we explore the epidemiological evidence supporting these associations and link to mechanistic insights. The long-term consequences of childhood RTIs and the comprehensive role of the microbiota at various stages in RTI pathogenesis call for early life preventative and therapeutic interventions to promote respiratory health.
10.1016/j.chom.2020.07.004
Respiratory Viral Infection-Induced Microbiome Alterations and Secondary Bacterial Pneumonia.
Hanada Shigeo,Pirzadeh Mina,Carver Kyle Y,Deng Jane C
Frontiers in immunology
Influenza and other respiratory viral infections are the most common type of acute respiratory infection. Viral infections predispose patients to secondary bacterial infections, which often have a more severe clinical course. The mechanisms underlying post-viral bacterial infections are complex, and include multifactorial processes mediated by interactions between viruses, bacteria, and the host immune system. Studies over the past 15 years have demonstrated that unique microbial communities reside on the mucosal surfaces of the gastrointestinal tract and the respiratory tract, which have both direct and indirect effects on host defense against viral infections. In addition, antiviral immune responses induced by acute respiratory infections such as influenza are associated with changes in microbial composition and function ("dysbiosis") in the respiratory and gastrointestinal tract, which in turn may alter subsequent immune function against secondary bacterial infection or alter the dynamics of inter-microbial interactions, thereby enhancing the proliferation of potentially pathogenic bacterial species. In this review, we summarize the literature on the interactions between host microbial communities and host defense, and how influenza, and other acute respiratory viral infections disrupt these interactions, thereby contributing to the pathogenesis of secondary bacterial infections.
10.3389/fimmu.2018.02640
Effect of gut microbiota on LPS-induced acute lung injury by regulating the TLR4/NF-kB signaling pathway.
International immunopharmacology
Acute lung injury (ALI) is a common acute respiratory disease treated in the clinic. Intestinal microflora disorder affect lung diseases through the gut-lung axis. In this study, we explored the regulatory mechanism of the gut flora in the host defense against lipopolysaccharide (LPS)-induced ALI through the TLR4/NF-kB pathway by constructing a gut microflora dysbiosis-model with antibiotic administration and reconstruction of the intestinal microecology. Then, high-throughput sequencing was performed, and the levels of secreted IgA (sIgA), β-defensins, and Muc2 were measured to assess the gut flora and mucosal barrier. The expression of TLR4, NF-kB, TNF-α, IL-1β, oxidative stress and the lung wet/dry (W/D) ratio were evaluated to assess lung damage. Hematoxylin and eosin (HE) staining was performed to evaluate the damage to the gut and lung tissues. Accordingly, gut microbiota imbalance may regulate the TLR4/NF-kB signaling pathway in the lung immune system, activating oxidative stress in the lung and mediating lung injury through the regulation of the gut barrier. However, fecal microbiota transplantation (FMT) impairs the activity of the TLR4/NF-kB signaling pathway in the lung and decreases oxidative stress in animals with ALI by restoring the gut microecology. CONCLUSIONS: Our results indicated the protective effect of gut flora in regulating immunity of LPS-induced ALI by modulating the TLR4/NF-kB signaling pathway which may induce inflammation and oxidative stress.
10.1016/j.intimp.2020.107272
Role of lung and gut microbiota on lung cancer pathogenesis.
Zhao Yue,Liu Yuxia,Li Shuang,Peng Zhaoyun,Liu Xiantao,Chen Jun,Zheng Xin
Journal of cancer research and clinical oncology
BACKGROUND:Lung cancer is the leading cause of cancer-related deaths worldwide (Ferlay et al., Int J Cancer 136:E359-386, 2015). In addition, lung cancer is associated with the highest mortality among all cancer types (Wu et al., Exp Ther Med 16:3004-3010, 2018). Previous studies report that microbiota play an important role in lung cancer. Notably, changes in lung and gut microbiota, are associated with progression of lung cancer. Several studies report that lung and gut microbiome promote lung cancer initiation and development by modulating metabolic pathways, inhibiting the function of immune cells, and producing pro-inflammatory factors. In addition, some factors such as microbiota dysbiosis, affect production of bacteriotoxins, genotoxicity and virulence effect, therefore, they play a key role in cancer progression. These findings imply that lung and gut microbiome are potential markers and targets for lung cancer. However, the role of microbiota in development and progression of lung cancer has not been fully explored. PURPOSE:The aim of this study was to systemically review recent research findings on relationship of lung and gut microbiota with lung cancer. In addition, we explored gut-lung axis and potential mechanisms of lung and gut microbiota in modulating lung cancer progression. CONCLUSION:Pulmonary and intestinal flora influence the occurrence, development, treatment and prognosis of lung cancer, and will provide novel strategies for prevention, diagnosis, and treatment of lung cancer.
10.1007/s00432-021-03644-0
Toward a Deeper Understanding of Gut Microbiome in Depression: The Promise of Clinical Applicability.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
The emergence of the coronavirus disease 2019 pandemic has dramatically increased the global prevalence of depression. Unfortunately, antidepressant drugs benefit only a small minority of patients. Thus, there is an urgent need to develop new interventions. Accumulating evidence supports a causal relationship between gut microbiota dysbiosis and depression. To advance microbiota-based diagnostics and therapeutics of depression, a comprehensive overview of microbial alterations in depression is presented to identify effector microbial biomarkers. This procedure generated 215 bacterial taxa from humans and 312 from animal models. Compared to controls, depression shows significant differences in β-diversity, but no changes in microbial richness and diversity. Additionally, species-specific microbial changes are identified like increased Eggerthella in humans and decreased Acetatifactor in rodent models. Moreover, a disrupted microbiome balance and functional changes, characterized by an enrichment of pro-inflammatory bacteria (e.g., Desulfovibrio and Escherichia/Shigella) and depletion of anti-inflammatory butyrate-producing bacteria (e.g., Bifidobacterium and Faecalibacterium) are consistently shared across species. Confounding effects of geographical region, depression type, and intestinal segments are also investigated. Ultimately, a total of 178 species and subspecies probiotics are identified to alleviate the depressive phenotypes. Current findings provide a foundation for developing microbiota-based diagnostics and therapeutics and advancing microbiota-oriented precision medicine for depression.
10.1002/advs.202203707
Dysbiosis, malnutrition and enhanced gut-lung axis contribute to age-related respiratory diseases.
Saint-Criq Vinciane,Lugo-Villarino Geanncarlo,Thomas Muriel
Ageing research reviews
Older people are at an increased risk of developing respiratory diseases such as chronic obstructive pulmonary diseases, asthma, idiopathic pulmonary fibrosis or lung infections. Susceptibility to these diseases is partly due to the intrinsic ageing process, characterized by genomic, cellular and metabolic hallmarks and immunosenescence, and is associated with changes in the intestinal microbiota. Importantly, in the lungs, ageing is also associated with a dysbiosis and loss of resilience of the resident microbiota and alterations of the gut-lung axis. Notably, as malnutrition is often observed in the elderly, nutrition is one of the most accessible modifiable factors affecting both senescence and microbiota. This article reviews the changes affecting the lung and its resident microbiota during ageing, as well as the interconnections between malnutrition, senescence, microbiota, gut-lung axis and respiratory health. As the communication along the gut-lung axis becomes more permissive with ageing, this review also explores the evidence that the gut and lung microbiota are key players in the maintenance of healthy lungs, and as such, are potential targets for nutrition-based preventive strategies against lung disease in elderly populations.
10.1016/j.arr.2020.101235
Respiratory and Intestinal Microbiota in Pediatric Lung Diseases-Current Evidence of the Gut-Lung Axis.
International journal of molecular sciences
The intestinal microbiota is known to influence local immune homeostasis in the gut and to shape the developing immune system towards elimination of pathogens and tolerance towards self-antigens. Even though the lung was considered sterile for a long time, recent evidence using next-generation sequencing techniques confirmed that the lower airways possess their own local microbiota. Since then, there has been growing evidence that the local respiratory and intestinal microbiota play a role in acute and chronic pediatric lung diseases. The concept of the so-called gut-lung axis describing the mutual influence of local microbiota on distal immune mechanisms was established. The mechanisms by which the intestinal microbiota modulates the systemic immune response include the production of short-chain fatty acids (SCFA) and signaling through pattern recognition receptors (PRR) and segmented filamentous bacteria. Those factors influence the secretion of pro- and anti-inflammatory cytokines by immune cells and further modulate differentiation and recruitment of T cells to the lung. This article does not only aim at reviewing recent mechanistic evidence from animal studies regarding the gut-lung axis, but also summarizes current knowledge from observational studies and human trials investigating the role of the respiratory and intestinal microbiota and their modulation by pre-, pro-, and synbiotics in pediatric lung diseases.
10.3390/ijms23126791
Short Chain Fatty Acids: Fundamental mediators of the gut-lung axis and their involvement in pulmonary diseases.
Chemico-biological interactions
The human microbiota is fundamental to correct immune system development and balance. Dysbiosis, or microbial content alteration in the gut and respiratory tract, is associated with immune system dysfunction and lung disease development. The microbiota's influence on human health and disease is exerted through the abundance of metabolites produced by resident microorganisms, where short-chain fatty acids (SCFAs) represent the fundamental class. SCFAs are mainly produced by the gut microbiota through anaerobic fermentation of dietary fibers, and are known to influence the homeostasis, susceptibility to and outcome of many lung diseases. This article explores the microbial species found in healthy human gastrointestinal and respiratory tracts. We investigate factors contributing to dysbiosis in lung illness, and the gut-lung axis and its association with lung diseases, with a particular focus on the functions and mechanistic roles of SCFAs in these processes. The key focus of this review is a discussion of the main metabolites of the intestinal microbiota that contribute to host-pathogen interactions: SCFAs, which are formed by anaerobic fermentation. These metabolites include propionate, acetate, and butyrate, and are crucial for the preservation of immune homeostasis. Evidence suggests that SCFAs prevent infections by directly affecting host immune signaling. This review covers the various and intricate ways through which SCFAs affect the immune system's response to infections, with a focus on pulmonary diseases including chronic obstructive pulmonary diseases, asthma, lung cystic fibrosis, and tuberculosis. The findings reviewed suggest that the immunological state of the lung may be indirectly influenced by elements produced by the gut microbiota. SCFAs represent valuable potential therapeutic candidates in this context.
10.1016/j.cbi.2022.110231
Thirty Years of Lactobacillus rhamnosus GG: A Review.
Capurso Lucio
Journal of clinical gastroenterology
Lactobacillus rhamnosus GG (LGG) was the first strain belonging to the genus Lactobacillus to be patented in 1989 thanks to its ability to survive and to proliferate at gastric acid pH and in medium containing bile, and to adhere to enterocytes. Furthermore LGG is able to produces both a biofilm that can mechanically protect the mucosa, and different soluble factors beneficial to the gut by enhancing intestinal crypt survival, diminishing apoptosis of the intestinal epithelium, and preserving cytoskeletal integrity. Moreover LGG thanks to its lectin-like protein 1 and 2 inhibits some pathogens such as Salmonella species. Finally LGG is able to promote type 1 immune-responsiveness by reducing the expression of several activation and inflammation markers on monocytes and by increasing the production of interleukin-10, interleukin-12 and tumor necrosis factor-α in macrophages. A large number of research data on Lactobacillus GG is the basis for the use of this probiotic for human health. In this review we have considered predominantly randomized controlled trials, meta-analysis, Cochrane Review, guide lines of Scientific Societies and anyway studies whose results were evaluated by means of relative risk, odds ratio, weighted mean difference 95% confidence interval. The effectiveness of LGG in gastrointestinal infections and diarrhea, antibiotic and Clostridium difficile associated diarrhea, irritable bowel syndrome, inflammatory bowel disease, respiratory tract infections, allergy, cardiovascular diseases, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, cystic fibrosis, cancer, elderly end sport were analyzed.
10.1097/MCG.0000000000001170
Antimicrobial peptides modulate lung injury by altering the intestinal microbiota.
Microbiome
BACKGROUND:Mammalian mucosal barriers secrete antimicrobial peptides (AMPs) as critical, host-derived regulators of the microbiota. However, mechanisms that support microbiota homeostasis in response to inflammatory stimuli, such as supraphysiologic oxygen, remain unclear. RESULTS:We show that supraphysiologic oxygen exposure to neonatal mice, or direct exposure of intestinal organoids to supraphysiologic oxygen, suppresses the intestinal expression of AMPs and alters intestinal microbiota composition. Oral supplementation of the prototypical AMP lysozyme to hyperoxia-exposed neonatal mice reduced hyperoxia-induced alterations in their microbiota and was associated with decreased lung injury. CONCLUSIONS:Our results identify a gut-lung axis driven by intestinal AMP expression and mediated by the intestinal microbiota that is linked to lung injury in newborns. Together, these data support that intestinal AMPs modulate lung injury and repair. Video Abstract.
10.1186/s40168-023-01673-0
Gut and airway microbiota dysbiosis and their role in COVID-19 and long-COVID.
Frontiers in immunology
The gut microbiota plays a crucial role in human health and disease. Gut dysbiosis is known to be associated with increased susceptibility to respiratory diseases and modifications in the immune response and homeostasis of the lungs (the so-called gut-lung axis). Furthermore, recent studies have highlighted the possible role of dysbiosis in neurological disturbances, introducing the notion of the "gut-brain axis." During the last 2 years, several studies have described the presence of gut dysbiosis during coronavirus disease 2019 (COVID-19) and its relationship with disease severity, SARS-CoV-2 gastrointestinal replication, and immune inflammation. Moreover, the possible persistence of gut dysbiosis after disease resolution may be linked to long-COVID syndrome and particularly to its neurological manifestations. We reviewed recent evidence on the association between dysbiosis and COVID-19, investigating the possible epidemiologic confounding factors like age, location, sex, sample size, the severity of disease, comorbidities, therapy, and vaccination status on gut and airway microbial dysbiosis in selected studies on both COVID-19 and long-COVID. Moreover, we analyzed the confounding factors strictly related to microbiota, specifically diet investigation and previous use of antibiotics/probiotics, and the methodology used to study the microbiota (α- and β-diversity parameters and relative abundance tools). Of note, only a few studies focused on longitudinal analyses, especially for long-term observation in long-COVID. Lastly, there is a lack of knowledge regarding the role of microbiota transplantation and other therapeutic approaches and their possible impact on disease progression and severity. Preliminary data seem to suggest that gut and airway dysbiosis might play a role in COVID-19 and in long-COVID neurological symptoms. Indeed, the development and interpretation of these data could have important implications for future preventive and therapeutic strategies.
10.3389/fimmu.2023.1080043
Gut microbiota and Covid-19- possible link and implications.
Dhar Debojyoti,Mohanty Abhishek
Virus research
Covid-19 is a major pandemic facing the world today caused by SARS-CoV-2 which has implications on our understanding of infectious diseases. Although, SARS-Cov-2 primarily causes lung infection through binding of ACE2 receptors present on the alveolar epithelial cells, yet it was recently reported that SARS-CoV-2 RNA was found in the faeces of infected patients. Interestingly, the intestinal epithelial cells particularly the enterocytes of the small intestine also express ACE2 receptors. Role of the gut microbiota in influencing lung diseases has been well articulated. It is also known that respiratory virus infection causes perturbations in the gut microbiota. Diet, environmental factors and genetics play an important role in shaping gut microbiota which can influence immunity. Gut microbiota diversity is decreased in old age and Covid-19 has been mainly fatal in elderly patients which again points to the role the gut microbiota may play in this disease. Improving gut microbiota profile by personalized nutrition and supplementation known to improve immunity can be one of the prophylactic ways by which the impact of this disease can be minimized in old people and immune-compromised patients. More trials may be initiated to see the effect of co-supplementation of personalized functional food including prebiotics/probiotics along with current therapies.
10.1016/j.virusres.2020.198018
The Role and Mechanism of Gut Microbiota in Pulmonary Arterial Hypertension.
Nutrients
Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease characterized by increased pulmonary vascular resistance, pulmonary vasoconstriction, and right ventricular hypertrophy. Recent developments in genomics and metabolomics have gradually revealed the roles of the gut microbiota (GM) and its metabolites in cardiovascular diseases. Accumulating evidence reveals that the GM plays important roles in the occurrence and development of PAH. Gut microbiota dysbiosis directly increases the gut permeability, thereby facilitating pathological bacterial translocation and allowing translocation of bacterial products such as lipopolysaccharides from the gut into circulation. This process aggravates pulmonary perivascular inflammation and exacerbates PAH development through the endothelial-mesenchymal transition. Additionally, a shift in the composition of PAH also affects the gut metabolites. Changes in gut metabolites, such as decreased short-chain fatty acids, increased trimethylamine N-oxide, and elevated serotonin, contribute to pulmonary perivascular inflammation and pulmonary vascular remodeling by activating several signaling pathways. Studies of the intestinal microbiota in treating pulmonary hypertension have strengthened linkages between the GM and PAH. Probiotic therapy and fecal microbiota transplantation may supplement existing PAH treatments. In this article, we provide new insight for diagnosing, preventing and treating PAH by adding to the current knowledge of the intestinal flora mechanisms and its metabolites efficacy involved in PAH.
10.3390/nu14204278
The treatment of Qibai Pingfei Capsule on chronic obstructive pulmonary disease may be mediated by Th17/Treg balance and gut-lung axis microbiota.
Journal of translational medicine
BACKGROUND:Chronic obstructive pulmonary disease (COPD), a prevalent, progressive respiratory disease, has become the third leading cause of death globally. Increasing evidence suggests that intestinal and pulmonary microbiota dysbiosis is associated with COPD. Researchers have shown that T helper (Th) 17/regulatory T (Treg) imbalance is involved in COPD. Qibai Pingfei Capsule (QBPF) is a traditional Chinese medicine used to treat COPD clinically in China. However, the effects of QBPF intervention on the Th17/Treg balance and microbiota in the gut and lung are still poorly understood. METHODS:This study divided the rats into three groups (n = 8): control, model, and QBPF group. After establishing the model of COPD for four weeks and administering of QBPF for two weeks, Th17 cells, Treg cells, their associated cytokines, transcription factors, and intestinal and pulmonary microbiota of rats were analyzed. Furthermore, the correlations between intestinal and pulmonary microbiota and between bacterial genera and pulmonary function and immune function were measured. RESULTS:The results revealed that QBPF could improve pulmonary function and contribute to the new balance of Th17/Treg in COPD rats. Meanwhile, QBPF treatment could regulate the composition of intestinal and pulmonary microbiota and improve community structure in COPD rats, suppressing the relative abundance of Coprococcus_2, Prevotella_9, and Blautia in the gut and Mycoplasma in the lung, but accumulating the relative abundance of Prevotellaceae_UCG_003 in the gut and Rikenellaceae_RC9_gut_group in the lung. Additionally, gut-lung axis was confirmed by the significant correlations between the intestinal and pulmonary microbiota. Functional analysis of microbiota showed amino acid metabolism was altered in COPD rats in the gut and lung. Spearman correlation analysis further enriched the relationship between the microbiota in the gut and lung and pulmonary function and immune function in COPD model rats. CONCLUSIONS:Our study indicated that the therapeutic effects of QBPF may be achieved by maintaining the immune cell balance and regulating the gut-lung axis microbiota, providing references to explore the potential biomarkers of COPD and the possible mechanism of QBPF to treat COPD.
10.1186/s12967-022-03481-w
Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications.
Gastroenterology
BACKGROUND & AIMS:We investigate interrelationships between gut microbes, metabolites, and cytokines that characterize COVID-19 and its complications, and we validate the results with follow-up, the Japanese 4D (Disease, Drug, Diet, Daily Life) microbiome cohort, and non-Japanese data sets. METHODS:We performed shotgun metagenomic sequencing and metabolomics on stools and cytokine measurements on plasma from 112 hospitalized patients with SARS-CoV-2 infection and 112 non-COVID-19 control individuals matched by important confounders. RESULTS:Multiple correlations were found between COVID-19-related microbes (eg, oral microbes and short-chain fatty acid producers) and gut metabolites (eg, branched-chain and aromatic amino acids, short-chain fatty acids, carbohydrates, neurotransmitters, and vitamin B6). Both were also linked to inflammatory cytokine dynamics (eg, interferon γ, interferon λ3, interleukin 6, CXCL-9, and CXCL-10). Such interrelationships were detected highly in severe disease and pneumonia; moderately in the high D-dimer level, kidney dysfunction, and liver dysfunction groups; but rarely in the diarrhea group. We confirmed concordances of altered metabolites (eg, branched-chain amino acids, spermidine, putrescine, and vitamin B6) in COVID-19 with their corresponding microbial functional genes. Results in microbial and metabolomic alterations with severe disease from the cross-sectional data set were partly concordant with those from the follow-up data set. Microbial signatures for COVID-19 were distinct from diabetes, inflammatory bowel disease, and proton-pump inhibitors but overlapping for rheumatoid arthritis. Random forest classifier models using microbiomes can highly predict COVID-19 and severe disease. The microbial signatures for COVID-19 showed moderate concordance between Hong Kong and Japan. CONCLUSIONS:Multiomics analysis revealed multiple gut microbe-metabolite-cytokine interrelationships in COVID-19 and COVID-19related complications but few in gastrointestinal complications, suggesting microbiota-mediated immune responses distinct between the organ sites. Our results underscore the existence of a gut-lung axis in COVID-19.
10.1053/j.gastro.2022.09.024
Nutrition, Immunosenescence, and Infectious Disease: An Overview of the Scientific Evidence on Micronutrients and on Modulation of the Gut Microbiota.
Advances in nutrition (Bethesda, Md.)
The immune system is key to host defense against pathogenic organisms. Aging is associated with changes in the immune system, with a decline in protective components (immunosenescence), increasing susceptibility to infectious disease, and a chronic elevation in low-grade inflammation (inflammaging), increasing the risk of multiple noncommunicable diseases. Nutrition is a determinant of immune cell function and of the gut microbiota. In turn, the gut microbiota shapes and controls the immune and inflammatory responses. Many older people show changes in the gut microbiota. Age-related changes in immune competence, low-grade inflammation, and gut dysbiosis may be interlinked and may relate, at least in part, to age-related changes in nutrition. A number of micronutrients (vitamins C, D, and E and zinc and selenium) play roles in supporting the function of many immune cell types. Some trials report that providing these micronutrients as individual supplements can reverse immune deficits in older people and/or in those with insufficient intakes. There is inconsistent evidence that this will reduce the risk or severity of infections including respiratory infections. Probiotic, prebiotic, or synbiotic strategies that modulate the gut microbiota, especially by promoting the colonization of lactobacilli and bifidobacteria, have been demonstrated to modulate some immune and inflammatory biomarkers in older people and, in some cases, to reduce the risk and severity of gastrointestinal and respiratory infections, although, again, the evidence is inconsistent. Further research with well-designed and well-powered trials in at-risk older populations is required to be more certain about the role of micronutrients and of strategies that modify the gut microbiota-host relationship in protecting against infection, especially respiratory infection.
10.1093/advances/nmac052
Alterations of the Gut Microbiota in Patients With Coronavirus Disease 2019 or H1N1 Influenza.
Gu Silan,Chen Yanfei,Wu Zhengjie,Chen Yunbo,Gao Hainv,Lv Longxian,Guo Feifei,Zhang Xuewu,Luo Rui,Huang Chenjie,Lu Haifeng,Zheng Beiwen,Zhang Jiaying,Yan Ren,Zhang Hua,Jiang Huiyong,Xu Qiaomai,Guo Jing,Gong Yiwen,Tang Lingling,Li Lanjuan
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
BACKGROUND:Coronavirus disease 2019 (COVID-19) is an emerging serious global health problem. Gastrointestinal symptoms are common in COVID-19 patients, and severe acute respiratory syndrome coronavirus 2 RNA has been detected in stool specimens. However, the relationship between the gut microbiome and disease remains to be established. METHODS:We conducted a cross-sectional study of 30 patients with COVID-19, 24 patients with influenza A(H1N1), and 30 matched healthy controls (HCs) to identify differences in the gut microbiota by 16S ribosomal RNA gene V3-V4 region sequencing. RESULTS:Compared with HCs, COVID-19 patients had significantly reduced bacterial diversity; a significantly higher relative abundance of opportunistic pathogens, such as Streptococcus, Rothia, Veillonella, and Actinomyces; and a lower relative abundance of beneficial symbionts. Five biomarkers showed high accuracy for distinguishing COVID-19 patients from HCs with an area under the curve (AUC) up to 0.89. Patients with H1N1 displayed lower diversity and different overall microbial composition compared with COVID-19 patients. Seven biomarkers were selected to distinguish the 2 cohorts (AUC = 0.94). CONCLUSIONS:The gut microbial signature of patients with COVID-19 was different from that of H1N1 patients and HCs. Our study suggests the potential value of the gut microbiota as a diagnostic biomarker and therapeutic target for COVID-19, but further validation is needed.
10.1093/cid/ciaa709
Gut Microbiota, in the Halfway between Nutrition and Lung Function.
Espírito Santo Christophe,Caseiro Catarina,Martins Maria João,Monteiro Rosário,Brandão Inês
Nutrients
The gut microbiota is often mentioned as a "forgotten organ" or "metabolic organ", given its profound impact on host physiology, metabolism, immune function and nutrition. A healthy diet is undoubtedly a major contributor for promoting a "good" microbial community that turns out to be crucial for a fine-tuned symbiotic relationship with the host. Both microbial-derived components and produced metabolites elicit the activation of downstream cascades capable to modulate both local and systemic immune responses. A balance between host and gut microbiota is crucial to keep a healthy intestinal barrier and an optimal immune homeostasis, thus contributing to prevent disease occurrence. How dietary habits can impact gut microbiota and, ultimately, host immunity in health and disease has been the subject of intense study, especially with regard to metabolic diseases. Only recently, these links have started to be explored in relation to lung diseases. The objective of this review is to address the current knowledge on how diet affects gut microbiota and how it acts on lung function. As the immune system seems to be the key player in the cross-talk between diet, gut microbiota and the lungs, involved immune interactions are discussed. There are key nutrients that, when present in our diet, help in gut homeostasis and lead to a healthier lifestyle, even ameliorating chronic diseases. Thus, with this review we hope to incite the scientific community interest to use diet as a valuable non-pharmacological addition to lung diseases management. First, we talk about the intestinal microbiota and interactions through the intestinal barrier for a better understanding of the following sections, which are the main focus of this article: the way diet impacts the intestinal microbiota and the immune interactions of the gut-lung axis that can explain the impact of diet, a key modifiable factor influencing the gut microbiota in several lung diseases.
10.3390/nu13051716
Links Between Inflammatory Bowel Disease and Chronic Obstructive Pulmonary Disease.
Raftery April L,Tsantikos Evelyn,Harris Nicola L,Hibbs Margaret L
Frontiers in immunology
Inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the gastrointestinal and respiratory tracts, respectively. These mucosal tissues bear commonalities in embryology, structure and physiology. Inherent similarities in immune responses at the two sites, as well as overlapping environmental risk factors, help to explain the increase in prevalence of IBD amongst COPD patients. Over the past decade, a tremendous amount of research has been conducted to define the microbiological makeup of the intestine, known as the intestinal microbiota, and determine its contribution to health and disease. Intestinal microbial dysbiosis is now known to be associated with IBD where it impacts upon intestinal epithelial barrier integrity and leads to augmented immune responses and the perpetuation of chronic inflammation. While much less is known about the lung microbiota, like the intestine, it has its own distinct, diverse microflora, with dysbiosis being reported in respiratory disease settings such as COPD. Recent research has begun to delineate the interaction or crosstalk between the lung and the intestine and how this may influence, or be influenced by, the microbiota. It is now known that microbial products and metabolites can be transferred from the intestine to the lung via the bloodstream, providing a mechanism for communication. While recent studies indicate that intestinal microbiota can influence respiratory health, intestinal dysbiosis in COPD has not yet been described although it is anticipated since factors that lead to dysbiosis are similarly associated with COPD. This review will focus on the gut-lung axis in the context of IBD and COPD, highlighting the role of environmental and genetic factors and the impact of microbial dysbiosis on chronic inflammation in the intestinal tract and lung.
10.3389/fimmu.2020.02144
The respiratory microbiota alpha-diversity in chronic lung diseases: first systematic review and meta-analysis.
Respiratory research
BACKGROUND:While there seems to be a consensus that a decrease in gut microbiome diversity is related to a decline in health status, the associations between respiratory microbiome diversity and chronic lung disease remain a matter of debate. We provide a systematic review and meta-analysis of studies examining lung microbiota alpha-diversity in patients with asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF) or bronchiectasis (NCFB), in which a control group based on disease status or healthy subjects is provided for comparison. RESULTS:We reviewed 351 articles on title and abstract, of which 27 met our inclusion criteria for systematic review. Data from 24 of these studies were used in the meta-analysis. We observed a trend that CF patients have a less diverse respiratory microbiota than healthy individuals. However, substantial heterogeneity was present and detailed using random-effects models, which limits the comparison between studies. CONCLUSIONS:Knowledge on respiratory microbiota is under construction, and for the moment, it seems that alpha-diversity measurements are not enough documented to fully understand the link between microbiota and health, excepted in CF context which represents the most studied chronic respiratory disease with consistent published data to link alpha-diversity and lung function. Whether differences in respiratory microbiota profiles have an impact on chronic respiratory disease symptoms and/or evolution deserves further exploration.
10.1186/s12931-022-02132-4
Microbiota Modulation of the Gut-Lung Axis in COVID-19.
Frontiers in immunology
COVID-19 is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and according to the World Health Organization (WHO), to date, SARS-CoV-2 has already infected more than 91.8 million people worldwide with 1,986,871 deaths. This virus affects mainly the respiratory system, but the gastrointestinal tract (GIT) is also a target, meanwhile SARS-CoV-2 was already detected in oesophagus, stomach, duodenum, rectum, and in fecal samples from COVID-19 patients. Prolonged GIT manifestations in COVID-19, mainly the diarrhea, were correlated with decreased richness and diversity of the gut microbiota, immune deregulation and delayed SARS-CoV-2 clearance. So, the bidirectional interactions between the respiratory mucosa and the gut microbiota, known as gut-lung axis, are supposed to be involved in the healthy or pathologic immune responses to SARS-CoV-2. In accordance, the intestinal dysbiosis is associated with increased mortality in other respiratory infections, due to an exacerbated inflammation and decreased regulatory or anti-inflammatory mechanisms in the lungs and in the gut, pointing to this important relationship between both mucosal compartments. Therefore, since the mucous membranes from the respiratory and gastrointestinal tracts are affected, in addition to dysbiosis and inflammation, it is plausible to assume that adjunctive therapies based on the modulation of the gut microbiota and re-establishment of eubiosis conditions could be an important therapeutic approach for constraining the harmful consequences of COVID-19. Then, in this review, we summarized studies showing the persistence of SARS-CoV-2 in the gastrointestinal system and the related digestive COVID-19 manifestations, in addition to the literature demonstrating nasopharyngeal, pulmonary and intestinal dysbiosis in COVID-19 patients. Lastly, we showed the potential beneficial role of probiotic administration in other respiratory infections, and discuss the possible role of probiotics as an adjunctive therapy in SARS-CoV-2 infection.
10.3389/fimmu.2021.635471
Gut microbiota: A new insight into lung diseases.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
The human gut microbiota is a complex ecosystem involved in the metabolism, immunity, and health of the host. The microbiome plays a key role in the development of the host's innate and adaptive immune system, while the immune system orchestrates the maintenance of host-microbe symbiosis. Lung diseases are usually accompanied by dysbiosis of the intestinal flora and an immune-inflammatory response. The intestinal flora and its metabolites are directly or indirectly involved in the immune regulation of the host in lung disease. However, the exact mechanism of action of the gut-lung axis crosstalk remains unclear. This review is aimed to summarize the latest advances in gut microbiota and their metabolites in typical lung diseases, such as pulmonary hypertension, COPD, and lung cancer. Especially COVID-19, a problem troubling the world, is also discussed in it. Moreover, it is concentrated on the action mechanisms between the identified gut microbiota or their metabolites and the specific lung diseases, and on the link among the gut microbiota, its metabolites, and immune regulation, which could be used as a breakthrough to find new mechanisms and targets for some diseases without specific therapeutic drugs in clinic. It is also discussed a new therapeutic tool "drug-bacterial interaction" and the potential of therapeutic applications in clinic. This review would provide a clear direction for future research on gut microbiota and lung diseases, and propose a new therapeutic strategy targeting "drug-bacterial interaction" in clinic.
10.1016/j.biopha.2022.113810
The microbiota in pneumonia: From protection to predisposition.
Thibeault Charlotte,Suttorp Norbert,Opitz Bastian
Science translational medicine
Mucosal surfaces of the upper respiratory tract and gut are physiologically colonized with their own collection of microbes, the microbiota. The normal upper respiratory tract and gut microbiota protects against pneumonia by impeding colonization by potentially pathogenic bacteria and by regulating immune responses. However, antimicrobial therapy and critical care procedures perturb the microbiota, thus compromising its function and predisposing to lung infections (pneumonia). Interindividual variations and age-related alterations in the microbiota also affect vulnerability to pneumonia. We discuss how the healthy microbiota protects against pneumonia and how host factors and medical interventions alter the microbiota, thus influencing susceptibility to pneumonia.
10.1126/scitranslmed.aba0501
Indole-3-Acetic Acid Alters Intestinal Microbiota and Alleviates Ankylosing Spondylitis in Mice.
Shen Jun,Yang Lianjun,You Ke,Chen Tao,Su Zhihai,Cui Zhifei,Wang Min,Zhang Weicong,Liu Bin,Zhou Kai,Lu Hai
Frontiers in immunology
Ankylosing spondylitis (AS) is a systemic, chronic, and inflammatory autoimmune disease associated with the disorder of intestinal microbiota. Unfortunately, effective therapies for AS are lacking. Recent evidence has indicated that indole-3-acetic acid (IAA), an important microbial tryptophan metabolite, can modulate intestinal homeostasis and suppress inflammatory responses. However, reports have not examined the protective effects of IAA against AS. In this study, we investigated the protective effects and underlying mechanisms through which IAA acts against AS. We constructed a proteoglycan (PG)-induced AS mouse model and administered IAA (50 mg/kg body weight) by intraperitoneal injection daily for 4 weeks. The effects of IAA on AS mice were evaluated by examining disease severity, intestinal barrier function, aryl hydrocarbon receptor (AhR) pathway, T-helper 17 (Th17)/T regulatory (Treg) balance, and inflammatory cytokine levels. The intestinal microbiota compositions were profiled through whole-genome sequencing. We observed that IAA decreased the incidence and severity of AS in mice, inhibited the production of pro-inflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-6, IL-17A, and IL-23), promoted the production of the anti-inflammatory cytokine IL-10, and reduced the ratios of pro-/anti- inflammatory cytokines. IAA ameliorated pathological changes in the ileum and improved intestinal mucosal barrier function. IAA also activated the AhR pathway, upregulated the transcription factor forehead box protein P3 (FoxP3) and increased Treg cells, and downregulated the transcription factors retinoic acid receptor-related orphan receptor gamma t (RORγt) and signal transducer and activator of transcription 3 (STAT3) and decreased Th17 cells. Furthermore, IAA altered the composition of the intestinal microbiota composition by increasing Bacteroides and decreasing Proteobacteria and Firmicutes, in addition to increasing the abundances of and . In conclusion, IAA exerted several protective effects against PG-induced AS in mice, which was mediated by the restoration of balance among the intestinal microbial community, activating the AhR pathway, and inhibiting inflammation. IAA might represent a novel therapeutic approach for AS.
10.3389/fimmu.2022.762580
Emerging pathogenic links between microbiota and the gut-lung axis.
Budden Kurtis F,Gellatly Shaan L,Wood David L A,Cooper Matthew A,Morrison Mark,Hugenholtz Philip,Hansbro Philip M
Nature reviews. Microbiology
The microbiota is vital for the development of the immune system and homeostasis. Changes in microbial composition and function, termed dysbiosis, in the respiratory tract and the gut have recently been linked to alterations in immune responses and to disease development in the lungs. In this Opinion article, we review the microbial species that are usually found in healthy gastrointestinal and respiratory tracts, their dysbiosis in disease and interactions with the gut-lung axis. Although the gut-lung axis is only beginning to be understood, emerging evidence indicates that there is potential for manipulation of the gut microbiota in the treatment of lung diseases.
10.1038/nrmicro.2016.142
The Bidirectional Gut-Lung Axis in Chronic Obstructive Pulmonary Disease.
American journal of respiratory and critical care medicine
Epidemiological studies indicate that chronic obstructive pulmonary disease (COPD) is associated with the incidence of changes in intestinal health. Cigarette smoking, as one of the major causes of COPD, can have an impact on the gastrointestinal system and promotes intestinal diseases. This points to the existence of gut-lung interactions, but an overview of the underlying mechanisms of the bidirectional connection between the lungs and the gut in COPD is lacking. The interaction between the lungs and the gut can occur through circulating inflammatory cells and mediators. Moreover, gut microbiota dysbiosis, observed in both COPD and intestinal disorders, can lead to a disturbed mucosal environment, including the intestinal barrier and immune system, and hence may negatively affect both the gut and the lungs. Furthermore, systemic hypoxia and oxidative stress that occur in COPD may also be involved in intestinal dysfunction and play a role in the gut-lung axis. In this review, we summarize data from clinical research, animal models, and studies that may explain the possible mechanisms of gut-lung interactions associated with COPD. Interesting observations on the possibility of promising future add-on therapies for intestinal dysfunction in patients with COPD are highlighted.
10.1164/rccm.202206-1066TR
The role of the lung microbiota and the gut-lung axis in respiratory infectious diseases.
Dumas Alexia,Bernard Lucie,Poquet Yannick,Lugo-Villarino Geanncarlo,Neyrolles Olivier
Cellular microbiology
The pulmonary microbial community, described only a few years ago, forms a discreet part of the human host microbiota. The airway microbiota has been found to be substantially altered in the context of numerous respiratory disorders; nonetheless, its role in health and disease is as yet only poorly understood. Another important parameter to consider is the gut-lung axis, where distal (gut) immune modulation during respiratory disease is mediated by the gut microbiota. The use of specific microbiota strains, termed "probiotics," with beneficial effects on the host immunity and/or against pathogens, has proven successful in the treatment of intestinal disorders and is also showing promise in the context of airway diseases. In this review, we highlight the beneficial role of the body's commensal bacteria during airway infectious diseases, including recent evidence highlighting their local (lung) or distal (gut) contribution in this process.
10.1111/cmi.12966
Intestinal Microbiota - An Unmissable Bridge to Severe Acute Pancreatitis-Associated Acute Lung Injury.
Frontiers in immunology
Severe acute pancreatitis (SAP), one of the most serious abdominal emergencies in general surgery, is characterized by acute and rapid onset as well as high mortality, which often leads to multiple organ failure (MOF). Acute lung injury (ALI), the earliest accompanied organ dysfunction, is the most common cause of death in patients following the SAP onset. The exact pathogenesis of ALI during SAP, however, remains unclear. In recent years, advances in the microbiota-gut-lung axis have led to a better understanding of SAP-associated lung injury (PALI). In addition, the bidirectional communications between intestinal microbes and the lung are becoming more apparent. This paper aims to review the mechanisms of an imbalanced intestinal microbiota contributing to the development of PALI, which is mediated by the disruption of physical, chemical, and immune barriers in the intestine, promotes bacterial translocation, and results in the activation of abnormal immune responses in severe pancreatitis. The pathogen-associated molecular patterns (PAMPs) mediated immunol mechanisms in the occurrence of PALI binding with pattern recognition receptors (PRRs) through the microbiota-gut-lung axis are focused in this study. Moreover, the potential therapeutic strategies for alleviating PALI by regulating the composition or the function of the intestinal microbiota are discussed in this review. The aim of this study is to provide new ideas and therapeutic tools for PALI patients.
10.3389/fimmu.2022.913178
The mutual interplay of gut microbiota, diet and human disease.
Illiano Placido,Brambilla Roberta,Parolini Cinzia
The FEBS journal
The intestinal milieu harbours the gut microbiota, consisting of a complex community of bacteria, archaea, fungi, viruses and protozoans that bring to the host organism an endowment of cells and genes more numerous than its own. In the last 10 years, mounting evidence has highlighted the prominent influence of the gut mutualistic bacterial communities on human health. Microbial colonization occurs alongside with immune system development and plays a role in intestinal physiology. The community of the gut microbiota does not undergo significant fluctuations throughout adult life. However, bacterial infections, antibiotic treatment, lifestyle, surgery and diet might profoundly affect it. Gut microbiota dysbiosis, defined as marked alterations in the amount and function of the intestinal microorganisms, is correlated with the aetiology of chronic noncommunicable diseases, ranging from cardiovascular, neurologic, respiratory and metabolic illnesses to cancer. In this review, we focus on the interplay among gut microbiota, diet and host to provide a perspective on the role of microbiota and their unique metabolites in the pathogenesis and/or progression of various human disorders. We discuss interventions based on microbiome studies, that is faecal microbiota transplantation, probiotics and prebiotics, to introduce the concept that correcting gut dysbiosis can ameliorate disease symptoms, thus offering a new approach towards disease treatment.
10.1111/febs.15217
The association between early-life gut microbiota and childhood respiratory diseases: a systematic review.
The Lancet. Microbe
Data from animal models suggest a role of early-life gut microbiota in lung immune development, and in establishing susceptibility to respiratory infections and asthma in humans. This systematic review summarises the association between infant (ages 0-12 months) gut microbiota composition measured by genomic sequencing, and childhood (ages 0-18 years) respiratory diseases (ie, respiratory infections, wheezing, or asthma). Overall, there was evidence that low α-diversity and relative abundance of particular gut-commensal bacteria genera (Bifidobacterium, Faecalibacterium, Ruminococcus, and Roseburia) are associated with childhood respiratory diseases. However, results were inconsistent and studies had important limitations, including insufficient characterisation of bacterial taxa to species level, heterogeneous outcome definitions, residual confounding, and small sample sizes. Large longitudinal studies with stool sampling during the first month of life and shotgun metagenomic approaches to improve bacterial and fungal taxa resolution are needed. Standardising follow-up times and respiratory disease definitions and optimising causal statistical approaches might identify targets for primary prevention of childhood respiratory diseases.
10.1016/S2666-5247(22)00184-7
The Gut-Lung Axis in Respiratory Disease.
Marsland Benjamin J,Trompette Aurélien,Gollwitzer Eva S
Annals of the American Thoracic Society
Host-microorganism interactions shape local cell functionality, immune responses, and can influence disease development. Evidence indicates that the impact of host-microbe interactions reaches far beyond the local environment, thus influencing responses in peripheral tissues. There is a vital cross-talk between the mucosal tissues of our body, as exemplified by intestinal complications during respiratory disease and vice versa. Although, mechanistically, this phenomenon remains poorly defined, the existence of the gut-lung axis and its implications in both health and disease could be profoundly important for both disease etiology and treatment. In this review, we highlight how changes in the intestinal microenvironment, with a particular focus on the intestinal microbiota, impact upon respiratory disease.
10.1513/AnnalsATS.201503-133AW
Intestinal microbiota in health and disease: role of bifidobacteria in gut homeostasis.
Tojo Rafael,Suárez Adolfo,Clemente Marta G,de los Reyes-Gavilán Clara G,Margolles Abelardo,Gueimonde Miguel,Ruas-Madiedo Patricia
World journal of gastroenterology
The pool of microbes inhabiting our body is known as "microbiota" and their collective genomes as "microbiome". The colon is the most densely populated organ in the human body, although other parts, such as the skin, vaginal mucosa, or respiratory tract, also harbour specific microbiota. This microbial community regulates some important metabolic and physiological functions of the host, and drives the maturation of the immune system in early life, contributing to its homeostasis during life. Alterations of the intestinal microbiota can occur by changes in composition (dysbiosis), function, or microbiota-host interactions and they can be directly correlated with several diseases. The only disease in which a clear causal role of a dysbiotic microbiota has been demonstrated is the case of Clostridium difficile infections. Nonetheless, alterations in composition and function of the microbiota have been associated with several gastrointestinal diseases (inflammatory bowel disease, colorectal cancer, or irritable bowel syndrome), as well as extra-intestinal pathologies, such as those affecting the liver, or the respiratory tract (e.g., allergy, bronchial asthma, and cystic fibrosis), among others. Species of Bifidobacterium genus are the normal inhabitants of a healthy human gut and alterations in number and composition of their populations is one of the most frequent features present in these diseases. The use of probiotics, including bifidobacteria strains, in preventive medicine to maintain a healthy intestinal function is well documented. Probiotics are also proposed as therapeutic agents for gastrointestinal disorders and other pathologies. The World Gastroenterology Organization recently published potential clinical applications for several probiotic formulations, in which species of lactobacilli are predominant. This review is focused on probiotic preparations containing Bifidobacterium strains, alone or in combination with other bacteria, which have been tested in human clinical studies. In spite of extensive literature on and research into this topic, the degree of scientific evidence of the effectiveness of probiotics is still insufficient in most cases. More effort need to be made to design and conduct accurate human studies demonstrating the efficacy of probiotics in the prevention, alleviation, or treatment of different pathologies.
10.3748/wjg.v20.i41.15163
The Gut Microbiota and Respiratory Diseases: New Evidence.
Chunxi Li,Haiyue Liu,Yanxia Lin,Jianbing Pan,Jin Su
Journal of immunology research
Human body surfaces, such as the skin, intestines, and respiratory and urogenital tracts, are colonized by a large number of microorganisms, including bacteria, fungi, and viruses, with the gut being the most densely and extensively colonized organ. The microbiome plays an essential role in immune system development and tissue homeostasis. Gut microbiota dysbiosis not only modulates the immune responses of the gastrointestinal (GI) tract but also impacts the immunity of distal organs, such as the lung, further affecting lung health and respiratory diseases. Here, we review the recent evidence of the correlations and underlying mechanisms of the relationship between the gut microbiota and common respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), lung cancer, and respiratory infection, and probiotic development as a therapeutic intervention for these diseases.
10.1155/2020/2340670