The Microbiota-Gut-Brain Axis

Physiological Reviews, Journal Year: 2019, Volume and Issue: 99(4), P. 1877 - 2013

Published: Aug. 28, 2019

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, past 15 yr have seen emergence microbiota (the trillions microorganisms within and on our bodies) as one key regulators function led to appreciation a distinct microbiota-gut-brain axis. This is gaining ever more traction fields investigating biological physiological basis psychiatric, neurodevelopmental, age-related, neurodegenerative disorders. brain communicate with each other via various routes including immune system, tryptophan metabolism, vagus nerve enteric nervous involving microbial metabolites such short-chain fatty acids, branched chain amino peptidoglycans. Many factors can influence composition early life, infection, mode birth delivery, use antibiotic medications, nature nutritional provision, environmental stressors, host genetics. At extreme diversity diminishes aging. Stress, particular, significantly impact at all stages life. Much recent work implicated gut many conditions autism, anxiety, obesity, schizophrenia, Parkinson’s disease, Alzheimer’s disease. Animal models paramount linking regulation fundamental neural processes, neurogenesis myelination, microbiome activation microglia. Moreover, translational human studies are ongoing will greatly enhance field. Future focus understanding mechanisms underlying attempt elucidate microbial-based intervention therapeutic strategies for neuropsychiatric

Language: Английский

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Interaction Between the Microbiota, Epithelia, and Immune Cells in the Intestine

Annual Review of Immunology, Journal Year: 2020, Volume and Issue: 38(1), P. 23 - 48

Published: April 26, 2020

The gastrointestinal tract harbors numerous commensal bacteria, referred to as the microbiota, that benefit host health by digesting dietary components and eliminating pathogens. intestinal microbiota maintains epithelial barrier integrity shapes mucosal immune system, balancing defense oral tolerance with microbial metabolites, components, attachment cells. To avoid aberrant responses, cells segregate from constructing chemical physical barriers, leading establishment of host-commensal mutualism. Furthermore, participate in maintenance a healthy community reinforce functions. Perturbations composition are commonly observed patients autoimmune diseases chronic inflammatory disorders. An understanding intimate interactions between cells, crucial for homeostasis might promote advances diagnostic therapeutic approaches various diseases.

Language: Английский

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Bile Acids Activated Receptors Regulate Innate Immunity

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 9

Published: Aug. 13, 2018

Once known exclusively for their role in nutrients absorption, primary bile acids, chenodeoxycholic and cholic acid, secondary deoxycholic lithocholic are signaling molecules, generated from cholesterol breakdown by the interaction of host intestinal microbiota, acting on several receptors including G Protein-Coupled Bile Acid Receptor 1 (GPBAR1 or TGR5) Farnesoid-X-Receptor (FXR). Both placed at interface immune system with microbiota highly represented cells innate immunity such as liver macrophages, dendritic natural killer (NK) T cells. Here, we review how GPBAR1 FXR modulate contribute to maintenance a tolerogenic phenotype entero-hepatic tissues, regulation might help explain beneficial effects exerted ligands metabolic disorders.

Language: Английский

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Gut microbiota-derived metabolites in the regulation of host immune responses and immune-related inflammatory diseases

Cellular and Molecular Immunology, Journal Year: 2021, Volume and Issue: 18(4), P. 866 - 877

Published: March 11, 2021

Language: Английский

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Impact of Bacterial Metabolites on Gut Barrier Function and Host Immunity: A Focus on Bacterial Metabolism and Its Relevance for Intestinal Inflammation

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: May 26, 2021

The diverse and dynamic microbial community of the human gastrointestinal tract plays a vital role in health, with gut microbiota supporting development function immune barrier. Crosstalk between microbiota-gut epithelium system determine individual health status, any crosstalk disturbance may lead to chronic intestinal conditions, such as inflammatory bowel diseases (IBD) celiac disease. Microbiota-derived metabolites are crucial mediators host-microbial interactions. Some beneficially affect host physiology short-chain fatty acids (SCFAs) secondary bile acids. Also, tryptophan catabolites responses, through binding aryl hydrocarbon receptor (AhR). AhR is abundantly present at mucosal surfaces when activated enhances epithelial barrier well regulatory responses. Exogenous diet-derived indoles (tryptophan) major source endogenous ligand precursors together SCFAs regulate inflammation by lowering stress immunity, IBD, expression downregulated metabolites. Here, we an overview microbiota-epithelium- immunity review how microbial-derived contribute homeostasis. discuss therapeutic potential bacterial for IBD disease essential dietary components fibers systemic

Language: Английский

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Molecular physiology of bile acid signaling in health, disease, and aging

Physiological Reviews, Journal Year: 2020, Volume and Issue: 101(2), P. 683 - 731

Published: Aug. 13, 2020

Several diseases and conditions have been associated with an uncontrolled rise in bile acid (BA) concentrations. This is often the case when tight feedback regulation of BA synthesis compromised to point that BAs become detrimental. their cognate receptors, farnesoid X receptor (FXR) Takeda G-protein 5 (TGR5), however, exert many beneficial roles as they enable tissues adapt environmental, nutritional, physiological cues. Over last two decades, mimetics targeting FXR, TGR5, or both, proven be efficacious alleviating chronic metabolic inflammatory disorders, such obesity, Type 2 diabetes (T2D), atherosclerosis non-alcoholic steatohepatitis (NASH). While several aspects signaling are still poorly understood, first therapeutics FXR making way into clinic treat liver diseases, primary biliary cholangitis (PBC) NASH. Drugs may, hence, a bright future continuing efforts on studying impact changing pathways humans will translate our emerging knowledge physiology model organisms clinical benefits.

Language: Английский

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Immune regulation by microbiome metabolites

Immunology, Journal Year: 2018, Volume and Issue: 154(2), P. 220 - 229

Published: March 23, 2018

Summary Commensal microbes and the host immune system have been co‐evolved for mutual regulation. Microbes regulate system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly via receptors other target molecules. Immune cells express metabolite‐specific such as P2X 7 , GPR 41, 43, 109A, aryl hydrocarbon receptor precursor (AhR), pregnane X ( PXR ), farnesoid FXR TGR 5 molecular targets. Microbial their form an extensive array signals to respond changes nutrition, health immunological status. As a consequence, metabolite contribute nutrient harvest from diet, metabolism system. Importantly, bidirectionally function promote both tolerance immunity effectively fight infection without developing inflammatory diseases. In pathogenic conditions, adverse effects observed well. Key immune‐regulatory functions metabolites, generated carbohydrates, proteins bile acids, are reviewed this article.

Language: Английский

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Functions of Gut Microbiota Metabolites, Current Status and Future Perspectives

Aging and Disease, Journal Year: 2022, Volume and Issue: 13(4), P. 1106 - 1106

Published: Jan. 1, 2022

Gut microbiota, a collection of microorganisms that live within gastrointestinal tract, provides crucial signaling metabolites for the physiological hosts. In healthy state, gut microbiota are helpful maintaining basic functions hosts, whereas disturbed production these can lead to numerous diseases such as metabolic diseases, cardiovascular neurodegenerative and cancer. Although there many reviews about specific mechanisms on is no comprehensive summarization metabolites. this Opinion, we discuss knowledge including types their ways acting targets. addition, summarize pathologic in health shaping composition nutrition. This paper be understanding roles thus provide guidance developing suitable therapeutic strategies combat microbial-driven improve health.

Language: Английский

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Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2022, Volume and Issue: 19(7), P. 432 - 450

Published: Feb. 14, 2022

Language: Английский

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Emerging roles of bile acids in mucosal immunity and inflammation

Mucosal Immunology, Journal Year: 2019, Volume and Issue: 12(4), P. 851 - 861

Published: April 5, 2019

Bile acids are cholesterol-derived surfactants that circulate actively between the liver and ileum classically recognized for emulsifying dietary lipids to facilitate absorption. More recent studies, however, have revealed new functions of bile acids; as pleotropic signaling metabolites regulate diverse metabolic inflammatory pathways in multiple cell types tissues through dynamic interactions with both germline-encoded host receptors microbiota. Accordingly, perturbed acid circulation and/or metabolism is now implicated pathogenesis cholestatic diseases, syndrome, colon cancer, bowel diseases (IBDs). Here, we discuss three-dimensional interplay acids, microbiota, mucosal immune system, focusing on mechanisms intestinal homeostasis inflammation. Although regulation only beginning be appreciated, targeting their cellular has already proven an important area drug discovery.

Language: Английский

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