How bile acids confer gut mucosal protection against bacteria

作者：Alan Frederick Hofmann, Lars Eckmann · 发表于：Proceedings of the National Academy of Sciences · 年份：2006 · DOI：10.1073/pnas.0600780103 · 被引用次数：242 · 研究领域：Drug Transport and Resistance Mechanisms、Clinical Nutrition and Gastroenterology、Pediatric Hepatobiliary Diseases and Treatments

Bile is a complex mixture of organic and inorganic molecules that is stored in the gallbladder and released into the proximal small intestine when a meal is eaten. Bile is both an excretory secretion, to eliminate cholesterol, bilirubin, and waste products, and a digestive secretion, to promote lipid absorption. The dominant organic constituents of bile are conjugated bile acids (also termed bile salts), glycine or taurine N-acyl amidated derivatives of bile acids that are formed from cholesterol in the liver cell. Bile acids are wedge-shaped, water soluble, amphipathic molecules with a hydrophobic side and a hydrophilic side. Adsorption of bile acid anions to lipid bilayers of dietary membrane lipids or fatty acids (derived by pancreatic lipase acting on triglyceride) increases the curvature of the bilayers, ultimately converting them to mixed micelles (1, 2). Such micellar solubilization of polar lipids greatly increases their rate of diffusion to the epithelial surface of the small intestine, and micellar solubilization is essential for the efficient absorption of lipids. Although most lipid absorption occurs in the proximal small intestine, conjugated bile acids themselves are not absorbed together with the solubilized lipids in the jejunum but pass to the distal small intestine, where they are efficiently absorbed by an active transport system present in the epithelium of the terminal ileum. Efficient intestinal reclamation of bile acids leads to the accumulation of a re...