Abstract:
Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates biliary secretion of lipids, endogenous metabolites and xenobiotics. In intestine, bile acids facilitate the digestion and absorption of dietary lipids and fat-soluble vitamins. Through activation of nuclear receptors and G protein-coupled receptors and interaction with gut microbiome, bile acids critically regulate host metabolism and innate and adaptive immunity, and are involved in the pathogenesis of cholestasis, metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), type-2 diabetes, and inflammatory bowel diseases (IBD). Bile acids and their derivatives have been developed as potential therapeutic agents for treating chronic metabolic and inflammatory liver diseases and gastrointestinal disorders. Significance Statement Bile acids facilitate biliary cholesterol solubilization and dietary lipid absorption, regulate host metabolism and immunity, and modulate gut microbiome. Targeting bile acid metabolism and signaling hold promise for treating metabolic and inflammatory diseases.
摘要:
胆汁酸是胆固醇分解代谢的最终产物。肝胆汁酸合成占人类每日胆固醇周转的主要部分。胆汁酸的胆汁分泌产生胆汁流动并促进脂质的胆汁分泌,内源性代谢物和外源性物质。在肠道中,胆汁酸促进膳食脂质和脂溶性维生素的消化和吸收。通过激活核受体和G蛋白偶联受体以及与肠道微生物组的相互作用,胆汁酸关键调节宿主代谢和先天和适应性免疫,并参与胆汁淤积的发病机理,代谢功能障碍相关的脂肪变性肝病(MASLD),酒精相关性肝病(ALD),2型糖尿病,和炎症性肠病(IBD)。胆汁酸及其衍生物已被开发为治疗慢性代谢和炎性肝病和胃肠道疾病的潜在治疗剂。意义声明胆汁酸促进胆汁胆固醇溶解和膳食脂质吸收,调节宿主的新陈代谢和免疫力,并调节肠道微生物组。靶向胆汁酸代谢和信号传导有望治疗代谢和炎性疾病。