Enterohepatic circulation of bile acids

Hepatocytes make primary bile acids (cholic and chenodeoxycholic acid) from cholesterol, at about 0.2–0.6 g a day, enough to replace faecal loss. CYP7A1 catalyses the rate-limiting step. The bile acids are conjugated with glycine or taurine and pumped into the canaliculi by the bile salt export pump (BSEP). Between meals they are stored in the gallbladder. After a meal, CCK delivers them to the duodenum, where they emulsify fat and form micelles.

In the terminal ileum, conjugated bile salts are actively taken up by the apical sodium-dependent bile acid transporter (ASBT, IBAT). They cross the enterocyte bound to ileal bile-acid-binding protein and leave through OSTα/β. A smaller amount of deconjugated bile acid is absorbed passively in the jejunum and colon. Bile acids travel in portal blood bound to albumin. Hepatocytes extract them very efficiently at first pass through NTCP and re-secrete them. The total pool is about 3 g and cycles about 4–12 times a day, roughly twice per meal.

Feedback. Bile acids activate the nuclear receptor FXR in ileal enterocytes, which releases FGF19 into the portal blood. FGF19 acts on hepatic FGFR4 to repress CYP7A1, and hepatic FXR acting through SHP does the same. This keeps synthesis matched to the amount returned. In the colon, bacteria deconjugate and 7α-dehydroxylate bile acids into secondary bile acids (deoxycholic and lithocholic). Lithocholate is poorly reabsorbed and is detoxified by sulfation. Other substances also recirculate enterohepatically, including urobilinogen and some drugs (ethinylestradiol, mycophenolate).