THE PECULIARITIES OF CLINICAL COURSE OF ATOPIC DERMATITIS AND THE COMORBID CONDITIONS IN EARLY INFANCY.
Petriashvili M,Jorjoliani L
Georgian medical news
Atopic dermatitis represents one of the most prevalent manifestations of atopy in children, which is distinguished by the early onset and high frequency of chronicity. The aim of this study was to study the clinical features of atopic dermatitis in early childhood and to evaluate comorbid conditions. The prospective research was conducted to study the cohort of 68 patients, who were developed the atopic dermatitis under 2 years of age. It was revealed, that the age of onset of the disease and the clinical severity was determined by the genetic predisposition on the mother's side. According to the clinical severity of the disease there were revealed the series of peculiarities especially in the case of moderate course: the high frequency of comorbid allergic pathology (rhinitis, conjunctivitis, urticaria, allergic gastritis) and the co-existing gastroenterological disorders (colic, constipation and foaming). The use of CoMISSas a non-invasive tool assumes the great importance in respect of making timely diagnosis of the allergy to cow's milk protein.
Influence of constipation on atopic dermatitis: A nationwide population-based cohort study in Taiwan.
Huang Yen-Chu,Wu Meng-Che,Wang Yu-Hsun,Wei James Cheng-Chung
International journal of clinical practice
BACKGROUND:Atopic dermatitis (AD) is the chronic inflammatory disorder that affects both in childhood and adulthood. Mounting evidence indicates that gut dysbiosis contributes to AD via the gut-skin axis. Constipation can result in alteration of the gut microflora. The clinical impact of constipation on AD has not been researched. Therefore, we aim to assess the risk of AD in constipated patients by the population-based cohort study. METHODS:We collected 85 554 constipated people and 85 554 people without constipation between 1999 and 2013 from the Taiwanese National Health Insurance Research Database. Propensity score analysis was administrated to match age, gender, comorbidities and medications at a ratio of 1:1. Multiple Cox regression analysis was utilised to evaluate the adjusted hazard ratio of AD. In addition, sensitivity tests and a stratified analysis were conducted. RESULTS:The incidence of AD was 4.9 per 1000 person-years in the constipation group, which was higher than the rate of 2.1 per 1000 person-years observed in the non-constipation group. After adjustment for age, gender, comorbidities, corticosteroids, antihistamine and antibiotics, constipated people had a 2.31-fold greater risk of AD compared with those without constipation (adjusted hazard ratio [aHR]: 2.31 (95% CI 2.17-2.46). Moreover, constipated people had a higher likelihood of AD, regardless of gender, comorbidities, as well as the usage of corticosteroids, antihistamines and antibiotics. CONCLUSION:Constipation is associated with a significantly risk factor of AD. Clinicians should be careful of the possibility of AD in constipated people. Further study is warranted to investigate the possible pathological mechanisms of this relationship.
10.1111/ijcp.13691
Combination of FLG mutations and SNPs of IL-17A and IL-19 influence on atopic dermatitis occurrence.
Klonowska Jolanta,Gleń Jolanta,Nowicki Roman J,Trzeciak Magdalena
Postepy dermatologii i alergologii
Introduction:Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease. A fresh look on the AD pathophysiology has focused on the skin barrier defect and immune dysfunctions. IL-17A and IL-19 seem to play role in AD pathogenesis. Aim:The aim was to investigate associations of SNPs of IL-17A (rs2275913) and IL-19 (rs22431188) with AD features, course and occurrence. Searching for prognostic panels composed of FLG (2282del4, R501X) mutations with IL-17A and IL-19 polymorphisms. Material and methods:Blood samples were collected from 239 patients with AD and 170 controls. Two SNPs, IL-17A and IL-19 and FLG null mutations were analyzed. PCR and RFLP restriction fragment length polymorphism analysis were used. SCORAD score to establish AD severity, VAS to estimate pruritus. Results:None polymorphisms of studied cytokines caused more frequent AD occurrence compared to controls. We found no associations between IL-17A and IL-19 gene polymorphisms and AD severity (respectively = 0.954; = 0.498), IgE level ( = 0.707; = 0.584), VAS ( = 0.953; = 0.478), concomitant asthma ( = 0.488, = 0.764). The G/G genotype in IL-17A (rs2275913) occurrence with coexisting 2282del4 FLG gene mutation increased the AD frequency 9 times ( = 0.0266). Conclusions:The SNPs of IL-17A rs2275913 and IL-19 rs22431188 SNP seem not to have influence on AD course and occurrence while studied alone. The coexistence of GG genotype of IL-17A and 2282del4 FLG mutation may play a role as prognostic AD factor.
10.5114/ada.2021.105412
Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis.
Palmer Colin N A,Irvine Alan D,Terron-Kwiatkowski Ana,Zhao Yiwei,Liao Haihui,Lee Simon P,Goudie David R,Sandilands Aileen,Campbell Linda E,Smith Frances J D,O'Regan Gráinne M,Watson Rosemarie M,Cecil Jo E,Bale Sherri J,Compton John G,DiGiovanna John J,Fleckman Philip,Lewis-Jones Sue,Arseculeratne Gehan,Sergeant Ann,Munro Colin S,El Houate Brahim,McElreavey Ken,Halkjaer Liselotte B,Bisgaard Hans,Mukhopadhyay Somnath,McLean W H Irwin
Nature genetics
Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.
10.1038/ng1767
Skin Microbiome in Atopic Dermatitis.
Acta dermato-venereologica
Atopic dermatitis is a common inflammatory skin disease with a complex pathogenesis that includes imbalanced immune system signalling, impaired skin barrier and enhanced Staphylococcus aureus skin colonization. The skin bacterial communities are characterized by increasing abundance of S. aureus, leading to reduced diversity compared with the bacterial communities on healthy skin, and increasing disease severity. In contrast, fungal communities are richer and more diverse on the skin of patients with atopic dermatitis, although distribution of the most common species is similar in patients and controls. Filaggrin deficiency in atopic dermatitis skin might be related to the enhanced skin colonization by S. aureus. In addition, S. aureus expressing variant virulence factors have been shown to elicit atopic dermatitis-like phenotypes in mice, indicating that specific S. aureus strains can induce flare-ups. This review aims to provide an overview of the recent literature on the skin microbiome in atopic dermatitis.
10.2340/00015555-3514
in immunomodulation: molecular mechanisms and potential applications.
Frontiers in immunology
Frequent use of hormones and drugs may be associated with side-effects. Recent studies have shown that probiotics have effects on the prevention and treatment of immune-related diseases. () had regulatory effects on intestinal microbiota, host epithelial cells, immune cells, cytokines, antibodies (Ab), toll-like receptors (TLRs), tryptophan (Try) metabolism, antioxidant enzymes, and expression of related genes, and exhibits antibacterial and anti-inflammatory effects, leading to alleviation of disease symptoms. Although the specific composition of the cell-free supernatant (CFS) of has not been clarified, its efficacy in animal models has drawn increased attention to its potential use. This review summarizes the effects of on intestinal flora and immune regulation, and discusses the feasibility of its application in atopic dermatitis (AD), asthma, necrotizing enterocolitis (NEC), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS), and provides insights for the prevention and treatment of immune-related diseases.
10.3389/fimmu.2023.1228754
Association of Toll-Like Cell Receptors TLR2 (p.Arg753GLN) and TLR4 (p.Asp299GLY) Polymorphisms with Indicators of General and Local Immunity in Patients with Atopic Dermatitis.
Tyurin Yury A,Shamsutdinov Anton F,Kalinin Nikolay N,Sharifullina Alsou A,Reshetnikova Irina D
Journal of immunology research
A whole group of polymorphisms of genes involved in the formation of the epidermal barrier, immune responses, and their regulation is important in the formation of atopic phenotype. The purpose of the study is to determine the relationship of polymorphisms of genes of Toll-like receptors TLR2 and TLR4 with clinical and immunological parameters in atopic dermatitis patients in a "case-control" study. Polymorphisms of genes TLR2 (p.Arg753Gln) and TLR4 (Asp299Gly) were detected by PCR. Parameters of the state of innate and adaptive immunity were assessed by the level of local production of sIgA, cytokine profile of blood serum for IL-4, IL-10, and IFN-. Biological samples from 50 people with allergic pathology, aged 4.5 to 35 years, and 100 healthy individuals (controls) were analyzed. Observed dysregulation of cytokine production (IL-4, IL-10) in patients with heterozygous polymorphic genotypes probably reflects an imbalance of Th1/Th2/Th17 regulation of immune system response in these individuals.
10.1155/2017/8493545
Association between polymorphisms and atopic dermatitis susceptibility: A systematic review and meta-analysis.
Gene
AIM:Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease that is closely linked to genetic factors. Previous studies have revealed numerous single nucleotide polymorphisms (SNPs) that been related to susceptibility to AD; however, the results are conflicting. Therefore, a meta-analysis was conducted to assess the associations of these polymorphisms and AD risk. MATERIAL AND METHODS:PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure databases were retrieved to identify eligible studies, with selected polymorphisms being reported in a minimum of three separate studies. The Newcastle-Ottawa Scale (NOS) was used to evaluate study quality. Review Manager 5.3 and STATA 14.0 were used to perform the meta-analysis. RESULTS:After screening, 64 studies involving 13 genes (24 SNPs) were selected for inclusion in the meta-analysis. Nine SNPs were positively correlated with AD susceptibility [filaggrin (FLG) R501X, FLG 2282del4, chromosome 11q13.5 rs7927894, interleukin (IL)-17A rs2275913, IL-18 -137 G/C, Toll-like receptor 2 (TLR2) rs5743708, TLR2 A-16934 T, serine protease inhibitor Kazal type-5 (SPINK5) Asn368Ser, interferon-γ (IFN-γ) T874A] and one was negatively associated with AD susceptibility (IL-4 -1098 T/G). The 14 remaining SNPs were not significantly associated with AD susceptibility. CONCLUSIONS:Nine SNPs that may be risk factors and one SNP that may be a protective factor for AD were identified, providing a reference for AD prediction, prevention, and therapy.
10.1016/j.gene.2024.148397
Toll-Like Receptors in Dermatology, Venereology, and Leprosy.
Gandhi Sneha,Ravindra K
Indian journal of dermatology
Toll-like receptors (TLRs) represent a family of Type I transmembrane proteins characterized by an extracellular leucine-rich repeat domain and a cytoplasmic domain. TLRs represent a conserved group of receptors which help the immune system to function properly. Different TLRs are associated with an array of skin diseases. TLR agonists and antagonists have great potential for the treatment of allergic and inflammatory diseases.
10.4103/ijd.IJD_486_17
Toll-like receptors: their roles in pathomechanisms of atopic dermatitis.
Frontiers in immunology
The skin functions as a physical barrier and represents the first line of the innate immune system. There is increasing evidence that toll-like receptors (TLRs) are involved in the pathomechanisms of not only infectious diseases, but also non-infectious inflammatory diseases. Interestingly, it has been demonstrated that TLRs recognize both exogenous threats, e.g. bacteria and viruses, and endogenous danger signals related to inflammation, cell necrosis, or tissue damage. Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease, which is associated with impaired skin barrier function, increased skin irritability to non-specific stimuli, and percutaneous sensitization. The impairment of skin barrier function in AD allows various stimuli, such as potential allergens and pathogens, to penetrate the skin and activate the innate immune system, including TLR signaling, which can lead to the development of adaptive immune reactions. In this review, I summarize the current understanding of the roles of TLR signaling in the pathogenesis of AD, with special emphasis on skin barrier function and inflammation.
10.3389/fimmu.2023.1239244
The Role of Toll-Like Receptors in Skin Host Defense, Psoriasis, and Atopic Dermatitis.
Sun Lixiang,Liu Wenjie,Zhang Ling-Juan
Journal of immunology research
As the key defense molecules originally identified in Drosophila, Toll-like receptor (TLR) superfamily members play a fundamental role in detecting invading pathogens or damage and initiating the innate immune system of mammalian cells. The skin, the largest organ of the human body, protects the human body by providing a critical physical and immunological active multilayered barrier against invading pathogens and environmental factors. At the first line of defense, the skin is constantly exposed to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), and TLRs, expressed in a cell type-specific manner by various skin cells, serve as key molecules to recognize PAMPs and DAMPs and to initiate downstream innate immune host responses. While TLR-initiated inflammatory responses are necessary for pathogen clearance and tissue repair, aberrant activation of TLRs will exaggerate T cell-mediated autoimmune activation, leading to unwanted inflammation, and the development of several skin diseases, including psoriasis, atopic dermatitis, systemic lupus erythematosus, diabetic foot ulcers, fibrotic skin diseases, and skin cancers. Together, TLRs are at the interface between innate immunity and adaptive immunity. In this review, we will describe current understanding of the role of TLRs in skin defense and in the pathogenesis of psoriasis and atopic dermatitis, and we will also discuss the development and therapeutic effect of TLR-targeted therapies.
10.1155/2019/1824624
Skin Barrier Abnormalities and Immune Dysfunction in Atopic Dermatitis.
Yang Gabsik,Seok Jin Kyung,Kang Han Chang,Cho Yong-Yeon,Lee Hye Suk,Lee Joo Young
International journal of molecular sciences
Atopic dermatitis (AD) is a common and relapsing skin disease that is characterized by skin barrier dysfunction, inflammation, and chronic pruritus. While AD was previously thought to occur primarily in children, increasing evidence suggests that AD is more common in adults than previously assumed. Accumulating evidence from experimental, genetic, and clinical studies indicates that AD expression is a precondition for the later development of other atopic diseases, such as asthma, food allergies, and allergic rhinitis. Although the exact mechanisms of the disease pathogenesis remain unclear, it is evident that both cutaneous barrier dysfunction and immune dysregulation are critical etiologies of AD pathology. This review explores recent findings on AD and the possible underlying mechanisms involved in its pathogenesis, which is characterized by dysregulation of immunological and skin barrier integrity and function, supporting the idea that AD is a systemic disease. These findings provide further insights for therapeutic developments aiming to repair the skin barrier and decrease inflammation.
10.3390/ijms21082867
Tryptophan, an important link in regulating the complex network of skin immunology response in atopic dermatitis.
Frontiers in immunology
Atopic dermatitis (AD) is a common chronic relapsing inflammatory skin disease, of which the pathogenesis is a complex interplay between genetics and environment. Although the exact mechanisms of the disease pathogenesis remain unclear, the immune dysregulation primarily involving the Th2 inflammatory pathway and accompanied with an imbalance of multiple immune cells is considered as one of the critical etiologies of AD. Tryptophan metabolism has long been firmly established as a key regulator of immune cells and then affect the occurrence and development of many immune and inflammatory diseases. But the relationship between tryptophan metabolism and the pathogenesis of AD has not been profoundly discussed throughout the literatures. Therefore, this review is conducted to discuss the relationship between tryptophan metabolism and the complex network of skin inflammatory response in AD, which is important to elucidate its complex pathophysiological mechanisms, and then lead to the development of new therapeutic strategies and drugs for the treatment of this frequently relapsing disease.
10.3389/fimmu.2023.1300378
A tryptophan metabolite of the skin microbiota attenuates inflammation in patients with atopic dermatitis through the aryl hydrocarbon receptor.
Yu Jinlei,Luo Yang,Zhu Zhenlai,Zhou Yufeng,Sun Licheng,Gao Jixin,Sun Jinlv,Wang Gang,Yao Xu,Li Wei
The Journal of allergy and clinical immunology
BACKGROUND:Previous studies have revealed significant alterations in the skin microbiota of patients with atopic dermatitis (AD) not only in diversity and composition but also in function, and the tryptophan (Trp) metabolic pathway is attenuated in the skin microbiota of patients with AD. OBJECTIVE:We sought to assess Trp metabolites on the skin surfaces of patients with AD and to explore the function of the microbial Trp metabolites in skin inflammation in patients with AD. METHODS:A gel-patch method was developed to collect metabolites on the skin surface, which were then assessed by using liquid chromatography-tandem mass spectrometry. A mouse model of calcipotriol (MC903)-induced AD-like dermatitis was used to evaluate the effects of microbial metabolites on AD, and aryl hydrocarbon receptor (AhR)-null mice and keratinocyte cultures were used to investigate the mechanism. RESULTS:Major microbial metabolites of Trp were detected on the skin surfaces of healthy subjects, and the level of indole-3-aldehyde (IAId), an indole derivative of Trp catabolism, was significantly lower in lesional and nonlesional skin of patients with AD than that of healthy subjects. IAId significantly attenuated skin inflammation in mice with MC903-induced AD-like dermatitis, and this effect was blocked by an AhR antagonist and abolished in AhR-null mice. Furthermore, IAId was found to inhibit the MC903-induced expression of thymic stromal lymphopoietin in keratinocytes in vivo and in vitro, which was mediated by binding of AhR to the thymic stromal lymphopoietin promoter. CONCLUSION:IAId, a skin microbiota-derived Trp metabolite, negatively regulated skin inflammation in patients with AD, revealing that skin microbiota play a significant functional role in the pathogenesis of AD.
10.1016/j.jaci.2018.11.036
Microbe-host interplay in atopic dermatitis and psoriasis.
Nature communications
Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.
10.1038/s41467-019-12253-y
mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axis.
Gut microbes
Gut microbial disturbance affects allergic diseases including asthma, atopic dermatitis (AD) via the aberrant immune response. Some Bifidobacterial species and strains have been reported to improve AD via modulating immune-microbe interactions in patients. However, the effective metabolites and mechanism of alleviating AD in bifidobacteria remain to be elucidated. This study aimed to explore the microbial metabolite and mechanism of to improve AD. Based on shotgun metagenomic sequencing and UHPLC Q-Exactive-MS targeted metabolic experiments and , we focused on tryptophan metabolism and indole derivatives, which are endogenous ligands for aryl hydrocarbon receptor (AHR). Indole-3-carbaldehyde (I3C), a tryptophan metabolite of CCFM1029 activated AHR-mediated immune signaling pathway to improve AD symptoms in animal and clinical experiments. CCFM1029 upregulated tryptophan metabolism and increased I3C to suppress aberrant T helper 2 type immune responses, but these benefits were eliminated by AHR antagonist CH223191. Furthermore, CCFM1029 reshaped gut microbial composition in AD patients, increased fecal and serum I3C, and maintained the abundance of related to tryptophan metabolism of gut microbiota. The results suggested that based on the interactions of the gut-skin axis, CCFM1029 upregulated tryptophan metabolism and produced I3C to activate AHR-mediated immune response, alleviating AD symptoms. Indole derivates, microbial metabolites of tryptophan, may be the potential metabolites of bifidobacteria to alleviate AD via the AHR signaling pathway.
10.1080/19490976.2022.2044723
Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis.
Furue Masutaka,Hashimoto-Hachiya Akiko,Tsuji Gaku
International journal of molecular sciences
The aryl hydrocarbon receptor (AHR)/AHR-nuclear translocator (ARNT) system is a sensitive sensor for small molecular, xenobiotic chemicals of exogenous and endogenous origin, including dioxins, phytochemicals, microbial bioproducts, and tryptophan photoproducts. AHR/ARNT are abundantly expressed in the skin. Once activated, the AHR/ARNT axis strengthens skin barrier functions and accelerates epidermal terminal differentiation by upregulating filaggrin expression. In addition, AHR activation induces oxidative stress. However, some AHR ligands simultaneously activate the nuclear factor-erythroid 2-related factor-2 (NRF2) transcription factor, which is a master switch of antioxidative enzymes that neutralizes oxidative stress. The immunoregulatory system governing T-helper 17/22 (Th17/22) and T regulatory cells (Treg) is also regulated by the AHR system. Notably, AHR agonists, such as tapinarof, are currently used as therapeutic agents in psoriasis and atopic dermatitis. In this review, we summarize recent topics on AHR related to atopic dermatitis and psoriasis.
10.3390/ijms20215424
Emerging Role of the IL-36/IL-36R Axis in Multiple Inflammatory Skin Diseases.
The Journal of investigative dermatology
IL-36 is a most recent member of the IL-1 cytokine family, primarily expressed at barrier sites of the body such as the skin, lungs, and intestine. It plays a vital role in inflammation and is implicated in the development of various cutaneous; intestinal; and pulmonary disorders, including psoriasis, inflammatory bowel disease, and chronic obstructive pulmonary disease. IL-36 comprises 4 isoforms: the proinflammatory IL-36α, IL-36β, and IL-36γ and the anti-inflammatory IL-36R antagonist. An imbalance between proinflammatory and anti-inflammatory IL-36 isoforms can contribute to the inflammatory fate of cells and tissues. IL-36 cytokines signal through an IL-36R heterodimer mediating their function through canonical signaling cacade, including the NF-B pathway. Prominent for its role in psoriasis, IL-36 has recently been associated with disease mechanisms in atopic dermatitis, hidradenitis suppurativa, neutrophilic dermatoses, autoimmune blistering disease, and Netherton syndrome. The major cutaneous source of IL-36 cytokines is keratinocytes, pointing to its role in the communication between the epidermis, innate (neutrophils, dendritic cells) immune system, and adaptive (T helper [Th]1 cells, Th17) immune system. Thus, cutaneous IL-36 signaling is crucial for the immunopathological outcome of various skin diseases. Consequently, the IL-36/IL-36R axis has recently been recognized as a promising drug target for the treatment of inflammatory disorders beyond psoriasis. This review summarizes the current update on IL-36 cytokines in inflammatory skin diseases.
10.1016/j.jid.2023.11.004
The Gut Microbiome as a Major Regulator of the Gut-Skin Axis.
Frontiers in microbiology
The adult intestine hosts a myriad of diverse bacterial species that reside mostly in the lower gut maintaining a symbiosis with the human habitat. In the current review, we describe the neoteric advancement in our comprehension of how the gut microbiota communicates with the skin as one of the main regulators in the gut-skin axis. We attempted to explore how this potential link affects skin differentiation and keratinization, its influence on modulating the cutaneous immune response in various diseases, and finally how to take advantage of this communication in the control of different skin conditions.
10.3389/fmicb.2018.01459
The gut-skin axis in health and disease: A paradigm with therapeutic implications.
O'Neill Catherine A,Monteleone Giovanni,McLaughlin John T,Paus Ralf
BioEssays : news and reviews in molecular, cellular and developmental biology
As crucial interface organs gut and skin have much in common. Therefore it is unsurprising that several gut pathologies have skin co-morbidities. Nevertheless, the reason for this remains ill explored, and neither mainstream gastroenterology nor dermatology research have systematically investigated the 'gut-skin axis'. Here, in reviewing the field, we propose several mechanistic levels on which gut and skin may interact under physiological and pathological circumstances. We focus on the gut microbiota, with its huge metabolic capacity, and the role of dietary components as potential principle actors along the gut-skin axis. We suggest that metabolites from either the diet or the microbiota are skin accessible. After defining open key questions around the nature of these metabolites, how they are sensed, and which cutaneous changes they can induce, we propose that understanding of these pathways will lead to novel therapeutic strategies based on targeting one organ to improve the health of the other.
10.1002/bies.201600008
Crosstalk between the Gut Microbiome and Colonic Motility in Chronic Constipation: Potential Mechanisms and Microbiota Modulation.
Nutrients
Chronic constipation (CC) is a highly prevalent and burdensome gastrointestinal disorder. Accumulating evidence highlights the link between imbalances in the gut microbiome and constipation. However, the mechanisms by which the microbiome and microbial metabolites affect gut movement remain poorly understood. In this review, we discuss recent studies on the alteration in the gut microbiota in patients with CC and the effectiveness of probiotics in treating gut motility disorder. We highlight the mechanisms that explain how the gut microbiome and its metabolism are linked to gut movement and how intestinal microecological interventions may counteract these changes based on the enteric nervous system, the central nervous system, the immune function, and the ability to modify intestinal secretion and the hormonal milieu. In particular, microbiota-based approaches that modulate the levels of short-chain fatty acids and tryptophan catabolites or that target the 5-hydroxytryptamine and Toll-like receptor pathways may hold therapeutic promise. Finally, we discuss the existing limitations of microecological management in treating constipation and suggest feasible directions for future research.
10.3390/nu14183704
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
Systematic review of the association between short-chain fatty acids and allergic diseases.
Allergy
We performed a systematic review to investigate the current evidence on the association between allergic diseases and short chain fatty acids (SCFAs), which are microbially produced and suggested as one mechanism on how gut microbiome affects the risk of allergic diseases. Medline, Embase and Web of Science were searched from data inception until September 2022. We identified 37 papers, of which 17 investigated prenatal or early childhood SCFAs and the development of allergic diseases in childhood, and 20 assessed SCFAs in patients with pre-existing allergic diseases. Study design, study populations, outcome definition, analysis method and reporting of the results varied between papers. Overall, there was some evidence showing that the three main SCFAs (acetate, propionate and butyrate) in the first few years of life had a protective effect against allergic diseases, especially for atopic dermatitis, wheeze or asthma and IgE-mediated food allergy in childhood. The association between each SCFA and allergic disease appeared to be different by disease and the age of assessment. Further research that can determine the potentially timing specific effect of each SCFA will be useful to investigate how SCFAs can be used in treatment or in prevention against allergic diseases.
10.1111/all.16065
Antibiotics-Induced Dysbiosis of Intestinal Microbiota Aggravates Atopic Dermatitis in Mice by Altered Short-Chain Fatty Acids.
Kim Ha Jung,Lee Seung Hwa,Hong Soo Jong
Allergy, asthma & immunology research
PURPOSE:Alterations in the intestinal microbiota in early life affects the development of atopic dermatitis (AD) in humans. This study aimed to further investigate the effects of gut dysbiosis in early life in an ovalbumin (OVA)-induced mouse model of AD. METHODS:The AD mouse model was developed by serial OVA sensitization and mice were treated with an antibiotic cocktail in their drinking water for 2 weeks before primary sensitization. Probiotics (, 1 × 10⁹ CFU) or 100 μL of fresh fecal supernatant were orally administered daily from 1 week before the first sensitization until the end of the study. RESULTS:The AD mice which received antibiotics had significantly aggravated phenotypes, including clinical score, transepidermal water loss, and histopathology, compared to those treated with healthy feces or probiotics. Total systemic immunoglobulin E production and skin interleukin (IL) 4 levels were significantly increased in the antibiotic-treated mice compared to the other groups. Antibiotic treatment also increased the levels of IL17 and group 3 innate lymphoid cells (ILC3) in the gut and significantly suppressed the production of short-chain fatty acids (SCFAs) and decreased the number FOXP3⁺ cells. CONCLUSIONS:Our results suggest that the status of the gut microbiota in early life in the mouse may play a crucial role in AD development through intestinal SCFA production through regulate the numbers of CD4⁺IL17⁺/CD4⁺FOXP3⁺ regulatory T cells and ILC3s.
10.4168/aair.2020.12.1.137
Bacterial Metabolites: A Link between Gut Microbiota and Dermatological Diseases.
International journal of molecular sciences
Dysbiosis has been identified in many dermatological conditions (e.g., psoriasis, atopic dermatitis, systemic lupus erythematosus). One of the ways by which the microbiota affect homeostasis is through microbiota-derived molecules (metabolites). There are three main groups of metabolites: short-chain fatty acids (SCFAs), tryptophan metabolites, and amine derivatives including trimethylamine N-oxide (TMAO). Each group has its own uptake and specific receptors through which these metabolites can exert their systemic function. This review provides up-to-date knowledge about the impact that these groups of gut microbiota metabolites may have in dermatological conditions. Special attention is paid to the effect of microbial metabolites on the immune system, including changes in the profile of the immune cells and cytokine disbalance, which are characteristic of several dermatological diseases, especially psoriasis and atopic dermatitis. Targeting the production of microbiota metabolites may serve as a novel therapeutic approach in several immune-mediated dermatological diseases.
10.3390/ijms24043494
A dysregulated sebum-microbial metabolite-IL-33 axis initiates skin inflammation in atopic dermatitis.
The Journal of experimental medicine
Microbial dysbiosis in the skin has been implicated in the pathogenesis of atopic dermatitis (AD); however, whether and how changes in the skin microbiome initiate skin inflammation, or vice versa, remains poorly understood. Here, we report that the levels of sebum and its microbial metabolite, propionate, were lower on the skin surface of AD patients compared with those of healthy individuals. Topical propionate application attenuated skin inflammation in mice with MC903-induced AD-like dermatitis by inhibiting IL-33 production in keratinocytes, an effect that was mediated through inhibition of HDAC and regulation of the AhR signaling pathway. Mice lacking sebum spontaneously developed AD-like dermatitis, which was improved by topical propionate application. A proof-of-concept clinical study further demonstrated the beneficial therapeutic effects of topical propionate application in AD patients. In summary, we have uncovered that the dysregulated sebum-microbial metabolite-IL-33 axis might play an initiating role in AD-related skin inflammation, thereby highlighting novel therapeutic strategies for the treatment of AD.
10.1084/jem.20212397
Gut-derived short-chain fatty acids modulate skin barrier integrity by promoting keratinocyte metabolism and differentiation.
Mucosal immunology
Barrier integrity is central to the maintenance of healthy immunological homeostasis. Impaired skin barrier function is linked with enhanced allergen sensitization and the development of diseases such as atopic dermatitis (AD), which can precede the development of other allergic disorders, for example, food allergies and asthma. Epidemiological evidence indicates that children suffering from allergies have lower levels of dietary fibre-derived short-chain fatty acids (SCFA). Using an experimental model of AD-like skin inflammation, we report that a fermentable fibre-rich diet alleviates systemic allergen sensitization and disease severity. The gut-skin axis underpins this phenomenon through SCFA production, particularly butyrate, which strengthens skin barrier function by altering mitochondrial metabolism of epidermal keratinocytes and the production of key structural components. Our results demonstrate that dietary fibre and SCFA improve epidermal barrier integrity, ultimately limiting early allergen sensitization and disease development.The Graphical Abstract was designed using Servier Medical Art images ( https://smart.servier.com ).
10.1038/s41385-022-00524-9
The role of short-chain fatty acids in inflammatory skin diseases.
Frontiers in microbiology
Short-chain fatty acids (SCFAs) are metabolites of gut microbes that can modulate the host inflammatory response, and contribute to health and homeostasis. Since the introduction of the gut-skin axis concept, the link between SCFAs and inflammatory skin diseases has attracted considerable attention. In this review, we have summarized the literature on the role of SCFAs in skin inflammation, and the correlation between SCFAs and inflammatory skin diseases, especially atopic dermatitis, urticaria, and psoriasis. Studies show that SCFAs are signaling factors in the gut-skin axis and can alleviate skin inflammation. The information presented in this review provides new insights into the molecular mechanisms driving gut-skin axis regulation, along with possible pathways that can be targeted for the treatment and prevention of inflammatory skin diseases.
10.3389/fmicb.2022.1083432