Bile acids and intestinal microbiota in autoimmune cholestatic liver diseases.

Abstract

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.