Enterohepatic bile acid recirculation

The enterohepatic bile acid recirculation is a highly efficient physiological process that recycles over 95% of bile acids daily between the liver, gallbladder, intestine, and back to the liver via portal circulation, conserving the bile acid pool of 2-4 grams in humans and minimizing de novo cholesterol-derived synthesis. Bile acids, synthesized primarily in hepatocytes via cholesterol 7α-hydroxylase (CYP7A1), are secreted into bile by the bile salt export pump (BSEP/ABCB11), aid intestinal lipid digestion, and are actively reabsorbed in the terminal ileum mainly by the apical sodium-dependent bile acid transporter (ASBT/SLC10A2), shuttled cytosolically by FABP6, and effluxed basolaterally by OSTα-OSTβ (SLC51A/SLC51B). Hepatic reuptake occurs via NTCP (SLC10A1) and OATPs (SLCO family), enabling reconjugation and resecretion. Dysregulation contributes to cholestatic liver diseases like primary biliary cholangitis and progressive familial intrahepatic cholestasis, where transporter mutations (e.g., ABCB11, SLC10A2) impair flow and cause toxic accumulation. Therapeutically, ASBT inhibitors like odevixibat and maralixibat are approved for cholestatic pruritus in Alagille syndrome and progressive familial intrahepatic cholestasis by interrupting recirculation to lower systemic bile acids, though challenges include gastrointestinal side effects and long-term nutritional impacts.

Other names

Bile acid enterohepatic circulationBile salt recyclingEnterohepatic circulation of bile acids

Inhibition of ileal ASBT (SLC10A2) to reduce bile acid reabsorption and promote fecal excretion, FXR agonism to regulate bile acid synthesis and transport, BSEP (ABCB11) inhibition or modulation for cholestasis