Bile Acid Signaling in Inflammatory Bowel Diseases
- PMID: 33289902
- PMCID: PMC7935738 (VSports注册入口)
- DOI: 10.1007/s10620-020-06715-3
V体育2025版 - Bile Acid Signaling in Inflammatory Bowel Diseases
Abstract
Bile acids are a group of chemically different steroids generated at the host/microbial interface. Indeed, while primary bile acids are the end-product of cholesterol breakdown in the host liver, secondary bile acids are the products of microbial metabolism VSports手机版. Primary and secondary bile acids along with their oxo derivatives have been identified as signaling molecules acting on a family of cell membrane and nuclear receptors collectively known as "bile acid-activated receptors. " Members of this group of receptors are highly expressed throughout the gastrointestinal tract and mediate the bilateral communications of the intestinal microbiota with the host immune system. The expression and function of bile acid-activated receptors FXR, GPBAR1, PXR, VDR, and RORγt are highly dependent on the structure of the intestinal microbiota and negatively regulated by intestinal inflammation. Studies from gene ablated mice have demonstrated that FXR and GPBAR1 are essential to maintain a tolerogenic phenotype in the intestine, and their ablation promotes the polarization of intestinal T cells and macrophages toward a pro-inflammatory phenotype. RORγt inhibition by oxo-bile acids is essential to constrain Th17 polarization of intestinal lymphocytes. Gene-wide association studies and functional characterizations suggest a potential role for impaired bile acid signaling in development inflammatory bowel diseases (IBD). In this review, we will focus on how bile acids and their receptors mediate communications of intestinal microbiota with the intestinal immune system, describing dynamic changes of bile acid metabolism in IBD and the potential therapeutic application of targeting bile acid signaling in these disorders. .
Keywords: Dysbiosis; FXR; GPBAR1; Innate immunity; Intestinal microbiota; RORγt. V体育安卓版.
Conflict of interest statement
Prof V体育ios版. Stefano Fiorucci, is listed as an inventor of some of the compounds mentioned in this paper: INT767 (Intercept Pharmaceuticals), BAR501 and BAR502 (Bar Pharmaceuticals) and has received research grants from BAR Pharamceuticals. The other authors do not have any conflict of interest to be disclosed.
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- Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem. 2003;72:137–174. doi: 10.1146/annurev.biochem.72.121801.161712. - DOI (VSports) - PubMed
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