Bile acids and their signaling pathways are increasingly recognized as potential therapeutic targets for cholestatic and metabolic liver diseases. This review summarizes new insights in bile acid physiology, focusing on regulatory roles of bile acids in the control of immune regulation and on effects of pharmacological modulators of bile acid signaling pathways in human liver disease. Recent mouse studies have highlighted the importance of the interactions between bile acids and gut microbiome. Interfering with microbiome composition may be beneficial for cholestatic and metabolic liver diseases by modulating formation of secondary bile acids, as different bile acid species have different signaling functions. Bile acid receptors such as FXR, VDR, and TGR5 are expressed in a variety of cells involved in innate as well as adaptive immunity, and specific microbial bile acid metabolites positively modulate immune responses of the host. Identification of Cyp2c70 as the enzyme responsible for the generation of hydrophilic mouse/rat-specific muricholic acids has allowed the generation of murine models with a human-like bile acid composition. These novel mouse models will aid to accelerate translational research on the (patho)physiological roles of bile acids in human liver diseases .

胆汁酸及其信号通路越来越被认为是胆汁淤积和代谢性肝病的潜在治疗靶点。本综述总结了胆汁酸生理学的新见解，重点关注胆汁酸在控制免疫调节中的调节作用以及胆汁酸信号通路的药理学调节剂在人类肝病中的作用。最近的小鼠研究强调了胆汁酸和肠道微生物组之间相互作用的重要性。通过调节次级胆汁酸的形成，干扰微生物组的组成可能对胆汁淤积和代谢性肝病有益，因为不同的胆汁酸种类具有不同的信号传导功能。FXR、VDR 和 TGR5 等胆汁酸受体在涉及先天免疫和适应性免疫的多种细胞中表达，和特定的微生物胆汁酸代谢物正向调节宿主的免疫反应。将 Cyp2c70 鉴定为负责产生亲水性小鼠/大鼠特异性鼠胆酸的酶已经允许产生具有类人胆汁酸成分的小鼠模型。这些新的小鼠模型将有助于加速胆汁酸在人类肝脏疾病中的（病理）生理作用的转化研究。