Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Nat Rev Gastroenterol Hepatol. 2024 May;21(5):348-364. doi: 10.1038/s41575-024-00896-2. Epub 2024 Feb 21.
The field of bile acid microbiology in the gastrointestinal tract is going through a current rebirth after a peak of activity in the late 1970s and early 1980s. This renewed activity is a result of many factors, including the discovery near the turn of the century that bile acids are potent signalling molecules and technological advances in next-generation sequencing, computation, culturomics, gnotobiology, and metabolomics. We describe the current state of the field with particular emphasis on questions that have remained unanswered for many decades in both bile acid synthesis by the host and metabolism by the gut microbiota. Current knowledge of established enzymatic pathways, including bile salt hydrolase, hydroxysteroid dehydrogenases involved in the oxidation and epimerization of bile acid hydroxy groups, the Hylemon-Bjӧrkhem pathway of bile acid C7-dehydroxylation, and the formation of secondary allo-bile acids, is described. We cover aspects of bile acid conjugation and esterification as well as evidence for bile acid C3-dehydroxylation and C12-dehydroxylation that are less well understood but potentially critical for our understanding of bile acid metabolism in the human gut. The physiological consequences of bile acid metabolism for human health, important caveats and cautionary notes on experimental design and interpretation of data reflecting bile acid metabolism are also explored.
肠道胆汁酸微生物学领域在 20 世纪 70 年代末和 80 年代初达到活动高峰期后,目前正在经历复兴。这种新的活动是多种因素共同作用的结果,包括本世纪初发现胆汁酸是有效的信号分子,以及在下一代测序、计算、宏基因组学、无菌动物和代谢组学方面的技术进步。我们描述了该领域的现状,特别强调了几十年来宿主胆汁酸合成和肠道微生物群代谢方面仍未得到解答的问题。目前对已建立的酶促途径的了解,包括胆汁盐水解酶、参与胆汁酸羟基氧化和差向异构化的羟甾族脱氢酶、胆汁酸 C7-脱羟化的 Hylemon-Bjӧrkhem 途径以及次级 allo-胆汁酸的形成,都进行了描述。我们涵盖了胆汁酸结合和酯化的各个方面,以及胆汁酸 C3-脱羟化和 C12-脱羟化的证据,这些方面的了解较少,但对我们理解人类肠道中的胆汁酸代谢可能至关重要。还探讨了胆汁酸代谢对人类健康的生理影响,以及反映胆汁酸代谢的实验设计和数据解释的重要注意事项和警示。