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    The Gut-Lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks. Enaud Raphaël,Prevel Renaud,Ciarlo Eleonora,Beaufils Fabien,Wieërs Gregoire,Guery Benoit,Delhaes Laurence 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
    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
    Microbes, metabolites, and the gut-lung axis. Dang Anh Thu,Marsland Benjamin J Mucosal immunology The microbiota plays an essential role in the education, development, and function of the immune system, both locally and systemically. Emerging experimental and epidemiological evidence highlights a crucial cross-talk between the intestinal microbiota and the lungs, termed the 'gut-lung axis'. Changes in the constituents of the gut microbiome, through either diet, disease or medical interventions (such as antibiotics) is linked with altered immune responses and homeostasis in the airways. The importance of the gut-lung axis has become more evident following the identification of several gut microbe-derived components and metabolites, such as short-chain fatty acids (SCFAs), as key mediators for setting the tone of the immune system. Recent studies have supported a role for SCFAs in influencing hematopoietic precursors in the bone marrow-a major site of innate and adaptive immune cell development. Here, we review the current understanding of host-microbe cross-talk along the gut-lung axis. We highlight the importance of SCFAs in shaping and promoting bone marrow hematopoiesis to resolve airway inflammation and to support a healthy homeostasis. 10.1038/s41385-019-0160-6
    The developing gut-lung axis: postnatal growth restriction, intestinal dysbiosis, and pulmonary hypertension in a rodent model. Wedgwood Stephen,Warford Cris,Agvatisiri Sharleen R,Thai Phung N,Chiamvimonvat Nipavan,Kalanetra Karen M,Lakshminrusimha Satyan,Steinhorn Robin H,Mills David A,Underwood Mark A Pediatric research BACKGROUND:Postnatal growth restriction (PNGR) in premature infants increases risk of pulmonary hypertension (PH). In a rodent model, PNGR causes PH, while combining PNGR and hyperoxia increases PH severity. We hypothesized that PNGR causes intestinal dysbiosis and that treatment with a probiotic attenuates PNGR-associated PH. METHOD:Pups were randomized at birth to room air or 75% oxygen (hyperoxia), to normal milk intake (10 pups/dam) or PNGR (17 pups/dam), and to probiotic Lactobacillus reuteri DSM 17938 or phosphate-buffered saline. After 14 days, PH was assessed by echocardiography and right ventricular hypertrophy (RVH) was assessed by Fulton's index (right ventricular weight/left ventricle + septal weight). The small bowel and cecum were analyzed by high-throughput 16S ribosomal RNA gene sequencing. RESULTS:PNGR with or without hyperoxia (but not hyperoxia alone) altered the microbiota of the distal small bowel and cecum. Treatment with DSM 17938 attenuated PH and RVH in pups with PNGR, but not hyperoxia alone. DSM 17938 treatment decreased α-diversity. The intestinal microbiota differed based on oxygen exposure, litter size, and probiotic treatment. CONCLUSION:PNGR causes intestinal dysbiosis and PH. Treatment with DSM 17938 prevents PNGR-associated RVH and PH. Changes in the developing intestine and intestinal microbiota impact the developing lung vasculature and RV. 10.1038/s41390-019-0578-2
    The Gut-Liver-Lung Axis. Modulation of the Innate Immune Response and Its Possible Role in Chronic Obstructive Pulmonary Disease. Young Robert P,Hopkins Raewyn J,Marsland Benjamin American journal of respiratory cell and molecular biology Evidence from epidemiological studies suggests that a diet high in fiber is associated with better lung function and reduced risk of chronic obstructive pulmonary disease (COPD). The mechanism for this benefit remains unknown, but, as fiber is not absorbed by the gut, this finding suggests that the gut may play an active role in pathogenic pathways underlying COPD. There is a growing awareness that aberrant activity of the innate immune system, characterized by increased neutrophil and macrophage activation, may contribute to the development or progression of COPD. Innate immunity is modulated in large part by the liver, where hepatic cells function in immune surveillance of the portal circulation, as well as providing a rich source of systemic inflammatory cytokines and immune mediators (notably, IL-6 and C-reactive protein). We believe that the beneficial effect of dietary fiber on lung function is through modulation of innate immunity and subsequent attenuation of the pulmonary response to inflammatory stimuli, most apparent in current or former smokers. We propose that the "gut-liver-lung axis" may play a modifying role in the pathogenesis of COPD. In this review, we summarize lines of evidence that include animal models, large prospective observational studies, and clinical trials, supporting the hypothesis that the gut-liver-lung axis plays an integral part in the pathogenic mechanisms underlying the pathogenesis of COPD. 10.1165/rcmb.2015-0250PS
    Alterations of intestinal flora and the effects of probiotics in children with recurrent respiratory tract infection. Li Ke-Liang,Wang Ben-Zhen,Li Zi-Pu,Li Yi-Lei,Liang Jing-Jing World journal of pediatrics : WJP BACKGROUND:Recurrent respiratory tract infection (RRTI) is a disease occurred frequently in preschool children. METHODS:A total of 120 RRTI children were randomly divided into active group, remission group, intervention group and control group, meanwhile 30 healthy children were selected as the healthy group. Children in the intervention group were given oral Bifidobaeterium tetravaccine tablets (Live) for 2 months, while the control group received routine treatment. Stool sample were detected to analyze the bacterial strains. The occurrence of respiratory tract infection (RTI) was compared between different groups during 1 year follow-up. RESULTS:Compared with the healthy group, the number of Bifidobacteria and Lactobacilli in the active group, remission group, intervention group and control group was significantly decreased (P < 0.05). The number of Bifidobacteria and Lactobacilli in the intervention group was significantly higher compared to other RRTI groups (P < 0.05). During the follow-up period, the average annual frequency of different acute RTI and use of antibiotics were significantly reduced (P < 0.05), the average duration of cough, fever and use of antibiotics at each episode were also significantly shortened (P < 0.05) in the intervention group compared to the control group. CONCLUSIONS:Children with RRTI are susceptible to intestinal flora imbalance. Oral probiotics can effectively improve the RRTI intestinal microecological balance in children and reduce the frequency of RTI. 10.1007/s12519-019-00248-0