Bile acids and the gut microbiota: metabolic interactions and impacts on disease

Nature Reviews Microbiology, Год журнала: 2022, Номер 21(4), С. 236 - 247

Опубликована: Окт. 17, 2022

Язык: Английский

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Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis

Cells, Год журнала: 2023, Номер 12(5), С. 793 - 793

Опубликована: Март 2, 2023

The gut microbiota, including bacteria, archaea, fungi, viruses and phages, inhabits the gastrointestinal tract. This commensal microbiota can contribute to regulation of host immune response homeostasis. Alterations have been found in many immune-related diseases. metabolites generated by specific microorganisms such as short-chain fatty acids (SCFAs), tryptophan (Trp) bile acid (BA) metabolites, not only affect genetic epigenetic but also impact metabolism cells, immunosuppressive inflammatory cells. cells (such tolerogenic macrophages (tMacs), dendritic (tDCs), myeloid-derived suppressive (MDSCs), regulatory T (Tregs), B (Breg) innate lymphocytes (ILCs)) Macs (iMacs), DCs, CD4 helper (Th)1, CD4Th2, Th17, natural killer (NK) NK neutrophils) express different receptors for SCFAs, Trp BA from microorganisms. Activation these promotes differentiation function inhibits causing reprogramming local systemic system maintain homeostasis individuals. We here will summarize recent advances understanding effects on homeostasis, especially functions

Язык: Английский

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Microbiota-mediated colonization resistance: mechanisms and regulation

Nature Reviews Microbiology, Год журнала: 2022, Номер 21(6), С. 347 - 360

Опубликована: Дек. 20, 2022

Язык: Английский

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Metabolic Messengers: bile acids

Nature Metabolism, Год журнала: 2022, Номер 4(4), С. 416 - 423

Опубликована: Март 25, 2022

Язык: Английский

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Microbial-derived metabolites as a risk factor of age-related cognitive decline and dementia

Molecular Neurodegeneration, Год журнала: 2022, Номер 17(1)

Опубликована: Июнь 17, 2022

A consequence of our progressively ageing global population is the increasing prevalence worldwide age-related cognitive decline and dementia. In absence effective therapeutic interventions, identifying risk factors associated with becomes increasingly vital. Novel perspectives suggest that a dynamic bidirectional communication system between gut, its microbiome, central nervous system, commonly referred to as microbiota-gut-brain axis, may be contributing factor for health disease. However, exact mechanisms remain undefined. Microbial-derived metabolites produced in gut can cross intestinal epithelial barrier, enter systemic circulation trigger physiological responses both directly indirectly affecting functions. Dysregulation this (i.e., dysbiosis) modulate cytotoxic metabolite production, promote neuroinflammation negatively impact cognition. review, we explore critical connections microbial-derived (secondary bile acids, trimethylamine-N-oxide (TMAO), tryptophan derivatives others) their influence upon function neurodegenerative disorders, particular interest less-explored role decline.

Язык: Английский

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Crosstalk between bile acid-activated receptors and microbiome in entero-hepatic inflammation

Trends in Molecular Medicine, Год журнала: 2022, Номер 28(3), С. 223 - 236

Опубликована: Янв. 21, 2022

Язык: Английский

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The Emerging Role of Bile Acids in the Pathogenesis of Inflammatory Bowel Disease

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Фев. 3, 2022

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory disorder of the gastrointestinal tract that arises due to complex interactions between host genetic risk factors, environmental and dysbiotic gut microbiota. Although metagenomic approaches have attempted characterise dysbiosis occurring in IBD, precise mechanistic pathways interlinking microbiota intestinal mucosa are still yet be unravelled. To deconvolute these interactions, more reductionist approach involving microbial metabolites has been suggested. Bile acids emerged as key class microbiota-associated perturbed IBD patients. In recent years, metabolomics studies revealed consistent defect bile acid metabolism with an increase primary reduction secondary This review explores evolving evidence specific interact epithelial immune cells contribute milieu seen IBD. Furthermore, we summarise linking intracellular known relevant including autophagy, apoptosis, inflammasome pathway. Finally, discuss how novel experimental bioinformatics could further advance our understanding role inform therapeutic strategies

Язык: Английский

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A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers

Science, Год журнала: 2023, Номер 380(6649)

Опубликована: Июнь 8, 2023

Antibiotics (ABX) compromise the efficacy of programmed cell death protein 1 (PD-1) blockade in cancer patients, but mechanisms underlying their immunosuppressive effects remain unknown. By inducing down-regulation mucosal addressin adhesion molecule (MAdCAM-1) ileum, post-ABX gut recolonization by Enterocloster species drove emigration enterotropic α4β7+CD4+ regulatory T 17 cells into tumor. These deleterious ABX were mimicked oral gavage species, genetic deficiency, or antibody-mediated neutralization MAdCAM-1 and its receptor, α4β7 integrin. contrast, fecal microbiota transplantation interleukin-17A prevented ABX-induced immunosuppression. In independent lung, kidney, bladder patient cohorts, low serum levels soluble had a negative prognostic impact. Thus, MAdCAM-1-α4β7 axis constitutes an actionable immune checkpoint immunosurveillance.

Язык: Английский

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Interactive Relationships between Intestinal Flora and Bile Acids

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(15), С. 8343 - 8343

Опубликована: Июль 28, 2022

The digestive tract is replete with complex and diverse microbial communities that are important for the regulation of multiple pathophysiological processes in humans animals, particularly those involved maintenance intestinal homeostasis, immunity, inflammation, tumorigenesis. diversity bile acids a result joint efforts host microflora. There bidirectional relationship between community that, while flora tightly modulates metabolism synthesis acids, acid pool composition affect homeostasis flora. Homeostatic imbalances systems may lead to development variety diseases, such as inflammatory bowel disease (IBD), colorectal cancer (CRC), hepatocellular carcinoma (HCC), type 2 diabetes (T2DM), polycystic ovary syndrome (PCOS). interactions be (in)directly pathogenesis these diseases.

Язык: Английский

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Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(11), С. 6046 - 6046

Опубликована: Май 27, 2022

Bile acids (BAs) are a group of amphiphilic molecules consisting rigid steroid core attached to hydroxyl with varying number, position, and orientation, hydrophilic side chain. While BAs act as detergents solubilize lipophilic nutrients in the small intestine during digestion absorption, they also hormones. Farnesoid X receptor (FXR) is nuclear that forms heterodimer retinoid α (RXRα), activated by enterohepatic circulation reabsorbed via transporters ileum colon, plays critical role regulating gene expression involved cholesterol, BA, lipid metabolism liver. The FXR/RXRα exists distal regulates production fibroblast growth factor (FGF) 15/FGF19, hormone traveling activates hepatic FGF 4 (FGFR4)-β-klotho complex metabolism, well those cell proliferation. Agonists for FXR analogs FGF15/19 currently recognized promising therapeutic target metabolic syndrome cholestatic diseases.

Язык: Английский

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