Bile acid signaling in metabolic and inflammatory diseases and drug development.

Abstract

Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates biliary secretion of lipids, endogenous metabolites and xenobiotics. In intestine, bile acids facilitate the digestion and absorption of dietary lipids and fat-soluble vitamins. Through activation of nuclear receptors and G protein-coupled receptors and interaction with gut microbiome, bile acids critically regulate host metabolism and innate and adaptive immunity, and are involved in the pathogenesis of cholestasis, metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), type-2 diabetes, and inflammatory bowel diseases (IBD). Bile acids and their derivatives have been developed as potential therapeutic agents for treating chronic metabolic and inflammatory liver diseases and gastrointestinal disorders. Significance Statement Bile acids facilitate biliary cholesterol solubilization and dietary lipid absorption, regulate host metabolism and immunity, and modulate gut microbiome. Targeting bile acid metabolism and signaling hold promise for treating metabolic and inflammatory diseases.