Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, USA.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, PR China.
Pharmacol Ther. 2022 Sep;237:108238. doi: 10.1016/j.pharmthera.2022.108238. Epub 2022 Jul 2.
The diversity, composition, and function of the bacterial community inhabiting the human gastrointestinal tract contributes to host health through its role in producing energy or signaling molecules that regulate metabolic and immunologic functions. Bile acids are potent metabolic and immune signaling molecules synthesized from cholesterol in the liver and then transported to the intestine where they can undergo metabolism by gut bacteria. The combination of host- and microbiota-derived enzymatic activities contribute to the composition of the bile acid pool and thus there can be great diversity in bile acid composition that depends in part on the differences in the gut bacteria species. Bile acids can profoundly impact host metabolic and immunological functions by activating different bile acid receptors to regulate signaling pathways that control a broad range of complex symbiotic metabolic networks, including glucose, lipid, steroid and xenobiotic metabolism, and modulation of energy homeostasis. Disruption of bile acid signaling due to perturbation of the gut microbiota or dysregulation of the gut microbiota-host interaction is associated with the pathogenesis and progression of metabolic disorders. The metabolic and immunological roles of bile acids in human health have led to novel therapeutic approaches to manipulate the bile acid pool size, composition, and function by targeting one or multiple components of the microbiota-bile acid-bile acid receptor axis.
人类胃肠道中栖息的细菌群落的多样性、组成和功能，通过产生能量或信号分子来调节代谢和免疫功能，从而促进宿主健康。胆汁酸是一种有效的代谢和免疫信号分子，由肝脏中的胆固醇合成，然后被运送到肠道，在那里可以被肠道细菌代谢。宿主和微生物衍生的酶活性的结合有助于胆汁酸库的组成，因此胆汁酸的组成可能存在很大的差异，这部分取决于肠道细菌物种的差异。胆汁酸可以通过激活不同的胆汁酸受体来深刻影响宿主的代谢和免疫功能，从而调节控制广泛复杂共生代谢网络的信号通路，包括葡萄糖、脂质、类固醇和外源性化合物代谢，以及能量平衡的调节。由于肠道微生物群的扰动或肠道微生物群-宿主相互作用的失调导致胆汁酸信号传导中断，与代谢紊乱的发病机制和进展有关。胆汁酸在人类健康中的代谢和免疫作用促使人们采用新的治疗方法，通过靶向微生物群-胆汁酸-胆汁酸受体轴的一个或多个成分来操纵胆汁酸库的大小、组成和功能。
