Role of bile acids in liver diseases mediated by the gut microbiome

Abstract

The intensive crosstalk between the liver and the intestine performs many essential functions. This crosstalk is important for natural immune surveillance, adaptive immune response regulation and nutrient metabolism and elimination of toxic bacterial metabolites. The interaction between the gut microbiome and bile acids is bidirectional. The gut microbiome regulates the synthesis of bile acids and their biological signaling activity and circulation via enzymes. Similarly, bile acids also shape the composition of the gut microbiome by modulating the host’s natural antibacterial defense and the intestinal immune system. The interaction between bile acids and the gut microbiome has been implicated in the pathophysiology of many intestinal and extra intestinal diseases, especially liver diseases. As essential mediators of the gut-liver crosstalk, bile acids regulate specific host metabolic pathways and modulate the inflammatory responses through farnesoid X-activated receptor and G protein-coupled bile acid receptor 1. Several clinical trials have demonstrated the signaling effects of bile acids in the context of liver diseases. We hypothesize the existence of a gut microbiome-bile acids-liver triangle and explore the potential therapeutic strategies for liver diseases targeting the triangle.

Keywords: Bile acids; Gut microbiome; Liver diseases; Farnesoid X-activated receptor; G protein-coupled bile acid receptor 1; Immune response

Core Tip: This review explores the interaction between the gut microbiome, bile acids and liver disease. Bile acids are involved in liver immune and inflammatory responses via the membrane receptor G protein-coupled bile acid receptor 1 and the intracellular farnesoid-X receptor. The interaction between the gut microbiome and bile acids can control host immunological homeostasis and inhibit liver inflammation.