Entrohepatic

Entrohepatic, more properly referred to as enterohepatic circulation, describes the recycling of bile acids and certain other compounds between the intestine and the liver. Bile acids are synthesized from cholesterol in liver cells, secreted into bile, stored in the gallbladder, and released into the small intestine to aid lipid digestion.

In the gut, most bile acids are reabsorbed in the terminal ileum. They are taken up by enterocytes via the apical sodium-dependent bile acid transporter (ASBT) and transported across the cells by the OSTα/OSTβ transporter back into the portal circulation, where they return to the liver. Hepatocytes then take them up again via transporters such as NTCP (sodium taurocholate cotransporting polypeptide) and OATPs (organic anion transporting polypeptides), allowing a continuing cycle.

The intestinal microbiota also modifies bile acids, converting primary bile acids into secondary bile acids through deconjugation and dehydroxylation. These microbial transformations influence signaling through receptors such as FXR (farnesoid X receptor) and TGR5, impacting lipid, glucose, and energy metabolism.

Entrohepatic circulation has significant pharmacological and clinical implications. Drugs that are excreted into bile or conjugated can undergo reabsorption, affecting their half-life and dosing. Disruptions in the cycle, such as ileal disease, ileal resection, or cholestasis, can cause bile acid malabsorption and diarrhea, while antibiotics or disease that alter gut microbiota can shift bile acid composition and recirculation.

Overall, enterohepatic circulation conserves the body’s bile acid pool, supports cholesterol homeostasis, and modulates multiple metabolic pathways through bile acid signaling.