Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
Division of Rheumatology, Department of Medicine, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA.
Autoimmun Rev. 2017 Sep;16(9):885-896. doi: 10.1016/j.autrev.2017.07.002. Epub 2017 Jul 8.
Autoimmune cholestatic liver diseases, including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), are manifested as an impairment of normal bile flow and excessive accumulation of potentially toxic bile acids. Endogenous bile acids are involved in the pathogenesis and progression of cholestasis. Consequently, chronic cholestasis affects the expression of bile acid transporters and nuclear receptors, and results in liver injury. Several lines of evidence suggest that intestinal microbiota plays an important role in the etiopathogenesis of cholestatic liver diseases by regulating metabolism and immune responses. However, progression of the disease may also affect the composition of gut microbiota, which in turn exacerbates the progression of cholestasis. In addition, the interaction between intestinal microbiota and bile acids is not unidirectional. Bile acids can shape the gut microbiota community, and in turn, intestinal microbes are able to alter bile acid pool. In general, gut microbiota actively communicates with bile acids, and together play an important role in the pathogenesis of PBC and PSC. Targeting the link between bile acids and intestinal microbiota offers exciting new perspectives for the treatment of those cholestatic liver diseases. This review highlights current understanding of the interactions between bile acids and intestinal microbiota and their roles in autoimmune cholestatic liver diseases. Further, we postulate a bile acids-intestinal microbiota-cholestasis triangle in the pathogenesis of autoimmune cholestatic liver diseases and potential therapeutic strategies by targeting this triangle.
自身免疫性胆汁淤积性肝病，包括原发性胆汁性胆管炎（PBC）和原发性硬化性胆管炎（PSC），表现为正常胆汁流动受损和潜在毒性胆汁酸的过度积累。内源性胆汁酸参与胆汁淤积的发病机制和进展。因此，慢性胆汁淤积会影响胆汁酸转运体和核受体的表达，导致肝损伤。有几条证据表明，肠道微生物群通过调节代谢和免疫反应在胆汁淤积性肝病的发病机制中起重要作用。然而，疾病的进展也可能影响肠道微生物群的组成，进而加剧胆汁淤积的进展。此外，肠道微生物群和胆汁酸之间的相互作用不是单向的。胆汁酸可以塑造肠道微生物群群落，反过来，肠道微生物也可以改变胆汁酸库。总的来说，肠道微生物群与胆汁酸积极沟通，共同在 PBC 和 PSC 的发病机制中发挥重要作用。针对胆汁酸和肠道微生物群之间的联系为治疗这些胆汁淤积性肝病提供了令人兴奋的新视角。本综述强调了目前对胆汁酸和肠道微生物群之间相互作用及其在自身免疫性胆汁淤积性肝病中的作用的理解。此外，我们假设在自身免疫性胆汁淤积性肝病的发病机制中存在一个胆汁酸-肠道微生物群-胆汁淤积的三角关系，并提出了针对该三角关系的潜在治疗策略。
