Bile acids and intestinal cholesterol

The "Bile acids and intestinal cholesterol" axis refers to the integrated physiological process of bile acid synthesis, secretion, and the absorption of dietary and biliary cholesterol (StatPearls: Bile Acid Synthesis and Metabolism, 2023). Bile acids are synthesized from cholesterol in the liver and secreted into the intestine to emulsify lipids, a process essential for the absorption of cholesterol via the Niemann-Pick C1-Like 1 (NPC1L1) transporter (PubMed: 14993912). The majority of these bile acids are subsequently reabsorbed in the terminal ileum by the Apical Sodium-dependent Bile Acid Transporter (ASBT, SLC10A2) and returned to the liver via enterohepatic circulation (UniProt: Q12908). This system is a primary therapeutic target for managing hypercholesterolemia, as inhibiting cholesterol absorption or sequestering bile acids in the gut forces the liver to utilize systemic cholesterol for de novo bile acid synthesis. Additionally, bile acids act as signaling molecules through receptors such as the Farnesoid X Receptor (FXR) and TGR5, which regulate metabolic pathways and are targets for treating cholestatic liver diseases and metabolic disorders (PubMed: 16299351). Pharmacological interventions in this pathway include NPC1L1 inhibitors like ezetimibe, bile acid sequestrants like colesevelam, and ASBT inhibitors like maralixibat. These therapies are critical for patients with dyslipidemia or rare cholestatic conditions where bile acid accumulation causes significant morbidity.

Other names

Enterohepatic circulation of bile acidsBile acid-cholesterol axisIntestinal cholesterol absorption pathwayBile acid metabolism

Inhibition of NPC1L1-mediated cholesterol absorption; sequestration of bile acids in the intestinal lumen to prevent reabsorption; inhibition of ASBT (SLC10A2) to block enterohepatic circulation; activation of FXR to regulate bile acid synthesis and transport.