Bile salt metabolism

Bile salt metabolism refers to the complex biochemical pathway responsible for the synthesis, secretion, transport, and recycling of bile acids, which are essential for dietary lipid absorption and systemic metabolic signaling (Chiang, J. Y. L., 2013, Comprehensive Physiology). This process begins in the liver with the conversion of cholesterol into primary bile acids, primarily regulated by the rate-limiting enzyme cholesterol 7-alpha-hydroxylase (CYP7A1) (StatPearls, 2023, Physiology, Bile Acids). Bile acids are then conjugated, stored in the gallbladder, and secreted into the duodenum to facilitate fat emulsification and the absorption of fat-soluble vitamins (Dawson, P. A., 2015, Journal of Lipid Research). The majority of bile acids are efficiently reclaimed from the terminal ileum by the apical sodium-dependent bile acid transporter (ASBT) and returned to the liver via the portal circulation, a process known as enterohepatic circulation (UniProt, 2024, SLC10A2). Dysregulation of this pathway is central to the pathogenesis of cholestatic liver diseases, gallstones, and metabolic disorders like nonalcoholic steatohepatitis (NASH) (Trauner, M., 2022, Gut). Therapeutic strategies targeting this pathway include farnesoid X receptor (FXR) agonists like obeticholic acid to reduce synthesis and ASBT inhibitors like odevixibat to increase fecal excretion (FDA, 2021, Bylvay Label).

Other names

Bile acid metabolismEnterohepatic circulation of bile acidsBile acid signaling pathwayBile acid synthesis and transport

Drugs modulate this pathway by acting as agonists for nuclear receptors like FXR to suppress bile acid synthesis, inhibiting intestinal transporters like ASBT to prevent reabsorption, or chemically sequestering bile acids in the gut to promote fecal excretion (Trauner, M., & Fuchs, C. D., 2022, Gut).