Enterohepatic

Entrohepatic circulation, or enterohepatic circulation, refers to the circulation of bile acids and certain other compounds between the liver and the intestine. Most notably, bile acids are synthesized in hepatocytes from cholesterol, conjugated to glycine or taurine, and secreted into bile. Bile is stored in the gallbladder and released into the duodenum in response to meals, where they emulsify fats and aid digestion.

In the terminal ileum, bile acids are reabsorbed primarily via the apical sodium-dependent bile acid transporter (ASBT), taken up by enterocytes, and returned to the liver via the portal venous system after being secreted into the basolateral side by OST alpha/beta transporters. Hepatocytes uptake bile acids through transporters such as NTCP and OATPs. This cycle conserves bile acids, maintains the overall bile acid pool, and provides negative feedback that helps regulate hepatic bile acid synthesis, notably through FXR signaling.

In the gut, gut bacteria deconjugate and 7α-dehydroxylate primary bile acids to form secondary bile acids (for example, deoxycholic and lithocholic acids). This microbial modification influences fat digestion, intestinal signaling, and the diversity of the bile acid pool.

Clinical relevance includes disruptions from ileal disease or resection, cholestasis, or antibiotic use, which can alter enterohepatic recirculation and affect lipid digestion or hepatic bile acid synthesis. The cycle also influences pharmacokinetics for drugs excreted in bile, potentially prolonging their half-life.