APC Microbiome Institute, University College Cork, Cork, Ireland; School of Microbiology, University College Cork, Cork, Ireland.
APC Microbiome Institute, University College Cork, Cork, Ireland; School of Microbiology, University College Cork, Cork, Ireland; School of Pharmacy, University College Cork, Cork, Ireland.
Mol Aspects Med. 2017 Aug;56:54-65. doi: 10.1016/j.mam.2017.06.002. Epub 2017 Jun 21.
Bile acids are synthesized from cholesterol in the liver and released into the intestine to aid the digestion of dietary lipids. The host enzymes that contribute to bile acid synthesis in the liver and the regulatory pathways that influence the composition of the total bile acid pool in the host have been well established. In addition, the gut microbiota provides unique contributions to the diversity of bile acids in the bile acid pool. Gut microbial enzymes contribute significantly to bile acid metabolism through deconjugation and dehydroxylation reactions to generate unconjugated bile acids and secondary bile acids. These microbial enzymes (which include bile salt hydrolase (BSH) and bile acid-inducible (BAI) enzymes) are essential for bile acid homeostasis in the host and represent a vital contribution of the gut microbiome to host health. Perturbation of the gut microbiota in disease states may therefore significantly influence bile acid signatures in the host, especially in the context of gastrointestinal or systemic disease. Given that bile acids are ligands for host cell receptors (including the FXR, TGR5 and Vitamin D Receptor) alterations to microbial enzymes and associated changes to bile acid signatures have significant consequences for the host. In this review we examine the contribution of microbial enzymes to the process of bile acid metabolism in the host and discuss the implications for microbe-host signalling in the context of C. difficile infection, inflammatory bowel disease and other disease states.
胆汁酸是在肝脏中从胆固醇合成的,并被释放到肠道中以帮助消化膳食脂质。有助于肝脏中胆汁酸合成的宿主酶以及影响宿主中总胆汁酸池组成的调节途径已经得到很好的确定。此外,肠道微生物群为胆汁酸池中的胆汁酸多样性提供了独特的贡献。肠道微生物酶通过去结合和去羟化反应显著促进胆汁酸代谢,从而生成非结合胆汁酸和次级胆汁酸。这些微生物酶(包括胆汁盐水解酶(BSH)和胆汁酸诱导(BAI)酶)对于宿主胆汁酸的动态平衡至关重要,代表了肠道微生物组对宿主健康的重要贡献。因此,疾病状态下肠道微生物群的失调可能会显著影响宿主中的胆汁酸特征,尤其是在胃肠道或全身性疾病的情况下。鉴于胆汁酸是宿主细胞受体的配体(包括 FXR、TGR5 和维生素 D 受体),微生物酶的改变以及与胆汁酸特征相关的改变对宿主有重大影响。在这篇综述中,我们检查了微生物酶对宿主胆汁酸代谢过程的贡献,并讨论了在艰难梭菌感染、炎症性肠病和其他疾病状态下微生物-宿主信号转导的意义。