Bile acid homeostasis pathway

Bile acid homeostasis pathways represent the integrated physiological systems that regulate the synthesis, transport, and recycling of bile acids between the liver and the intestine. This process, known as the enterohepatic circulation, is critical for the digestion and absorption of dietary fats and fat-soluble vitamins, while also serving as a major route for cholesterol elimination (Source: StatPearls, Bile Acid Metabolism). Bile acids function as potent signaling molecules that activate specific receptors, most notably the nuclear Farnesoid X receptor (FXR) and the membrane-bound G protein-coupled bile acid receptor 1 (TGR5), which coordinate metabolic responses in the liver, gut, and adipose tissue (Source: PubMed, PMID: 28456651). Dysregulation of these pathways leads to the accumulation of toxic bile acids, contributing to cholestatic liver diseases, metabolic syndrome, and inflammatory conditions (Source: NIH, LiverTox). Therapeutic strategies targeting these pathways include FXR agonists to reduce bile acid production and ASBT inhibitors to prevent their reabsorption, offering treatments for conditions like primary biliary cholangitis and pruritus in Alagille syndrome (Source: FDA, Odevixibat Label). However, pharmacological intervention must balance efficacy with side effects such as severe pruritus and alterations in lipid profiles (Source: Journal of Hepatology, PMID: 30220517).

Other names

Bile acid metabolismEnterohepatic circulation of bile acidsBile acid signaling pathway

Drugs targeting this pathway primarily act as agonists of the Farnesoid X receptor (FXR) to suppress bile acid synthesis via FGF19 signaling, or as inhibitors of the apical sodium-dependent bile acid transporter (ASBT) to block intestinal reabsorption and promote fecal excretion.