Department of Molecular Systems Biology, Helmholtz Center for Environmental Research, Leipzig, Germany.
Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
Immunol Rev. 2017 Sep;279(1):23-35. doi: 10.1111/imr.12579.
Bile salts are the water-soluble end products of hepatic cholesterol catabolism that are released into the duodenum and solubilize lipids due to their amphipathic structure. Bile salts also act as endogenous ligands for dedicated nuclear receptors that exert a plethora of biological processes, mostly related to metabolism. Bile salts are actively reclaimed in the distal part of the small intestine, released into the portal system, and subsequently extracted by the liver. This enterohepatic cycle is critically dependent on dedicated bile salt transporters. In the intestinal lumen, bile salts exert direct antimicrobial activity based on their detergent property and shape the gut microbiota. Bile salt metabolism by gut microbiota serves as a mechanism to counteract this toxicity and generates bile salt species that are distinct from those of the host. Innate immune cells of the liver play an important role in the early recognition and effector response to invading microbes. Bile salts signal primarily via the membrane receptor TGR5 and the intracellular farnesoid-x receptor, both present in innate immune cells. In this review, the interactions between bile salts, gut microbiota, and hepatic innate immunity are discussed.
胆汁盐是肝脏胆固醇分解代谢的水溶性终产物，它们具有两亲性结构，因此被释放到十二指肠中并溶解脂质。胆汁盐还作为内源性配体作用于特定的核受体，发挥多种生物学过程，主要与代谢有关。胆汁盐在小肠的远端被主动回收，释放到门静脉系统中，随后被肝脏提取。这种肠肝循环严重依赖于专门的胆汁盐转运蛋白。在肠腔中，胆汁盐基于其去污特性发挥直接的抗菌活性，并塑造肠道微生物群。肠道微生物群通过胆汁盐代谢来对抗这种毒性，并产生与宿主不同的胆汁盐种类。肝脏的固有免疫细胞在早期识别和对外来微生物的效应反应中发挥着重要作用。胆汁盐主要通过膜受体 TGR5 和细胞内法尼醇 X 受体（两者均存在于固有免疫细胞中）发出信号。在这篇综述中，讨论了胆汁盐、肠道微生物群和肝脏固有免疫之间的相互作用。
