Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, 33458, USA.
Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
Mucosal Immunol. 2019 Jul;12(4):851-861. doi: 10.1038/s41385-019-0162-4. Epub 2019 Apr 5.
Bile acids are cholesterol-derived surfactants that circulate actively between the liver and ileum and that are classically recognized for emulsifying dietary lipids to facilitate absorption. More recent studies, however, have revealed new functions of bile acids; as pleotropic signaling metabolites that regulate diverse metabolic and inflammatory pathways in multiple cell types and tissues through dynamic interactions with both germline-encoded host receptors and the microbiota. Accordingly, perturbed bile acid circulation and/or metabolism is now implicated in the pathogenesis of cholestatic liver diseases, metabolic syndrome, colon cancer, and inflammatory bowel diseases (IBDs). Here, we discuss the three-dimensional interplay between bile acids, the microbiota, and the mucosal immune system, focusing on the mechanisms that regulate intestinal homeostasis and inflammation. Although the functions of bile acids in mucosal immune regulation are only beginning to be appreciated, targeting bile acids and their cellular receptors has already proven an important area of new drug discovery.
胆汁酸是胆固醇衍生的表面活性剂,在肝脏和回肠之间循环活跃,经典地被认为可以乳化膳食脂肪,促进吸收。然而,最近的研究揭示了胆汁酸的新功能;作为多效信号代谢物,通过与种系编码的宿主受体和微生物群的动态相互作用,调节多种细胞类型和组织中的代谢和炎症途径。因此,胆汁酸循环和/或代谢紊乱现在与胆汁淤积性肝病、代谢综合征、结肠癌和炎症性肠病(IBD)的发病机制有关。在这里,我们讨论了胆汁酸、微生物群和黏膜免疫系统之间的三维相互作用,重点讨论了调节肠道内稳态和炎症的机制。尽管胆汁酸在黏膜免疫调节中的功能才刚刚开始被认识,但靶向胆汁酸及其细胞受体已经被证明是新药发现的一个重要领域。