美国哈佛医学院A. Sloan Devlin研究小组发现，肠道细菌在氢气存在下将糖皮质激素转化为孕激素。相关论文于2024年5月24日在线发表在《细胞》杂志上。
据悉，最近的研究表明，人类相关细菌与宿主产生的类固醇相互作用，但这种相互作用的机制和生理影响仍不清楚。
研究人员发现人类肠道细菌Gordonibacter pamelaeae和Eggerthella lenta通过21-脱羟基作用将丰富的胆汁皮质激素转化为孕激素，从而将一类免疫和代谢调节类固醇转化为一类性激素和神经类固醇。通过比较基因组学、同源表达和异源表达，研究人员发现了一个进行21-脱羟基化的细菌基因簇。研究人员还发现，肠道共生菌产生的氢气在促进21-脱羟基化过程中发挥了意想不到的作用，这表明氢气能调节肠道中的次级代谢。
某些细菌孕激素，包括别孕烷醇酮（即美国食品及药物管理局批准的治疗产后抑郁症的药物），在孕妇粪便中的含量大幅增加。因此，细菌将皮质激素转化为孕激素可能会影响宿主的生理机能，尤其是在怀孕和妇女健康方面。
附：英文原文
Title: Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas
Author: Megan D. McCurry, Gabriel D. D’Agostino, Jasmine T. Walsh, Jordan E. Bisanz, Ines Zalosnik, Xueyang Dong, David J. Morris, Joshua R. Korzenik, Andrea G. Edlow, Emily P. Balskus, Peter J. Turnbaugh, Jun R. Huh, A. Sloan Devlin
Issue&Volume: 2024-05-24
Abstract: Recent studies suggest that human-associated bacteria interact with host-producedsteroids, but the mechanisms and physiological impact of such interactions remainunclear. Here, we show that the human gut bacteria Gordonibacter pamelaeae and Eggerthella lenta convert abundant biliary corticoids into progestins through 21-dehydroxylation, therebytransforming a class of immuno- and metabo-regulatory steroids into a class of sexhormones and neurosteroids. Using comparative genomics, homologous expression, andheterologous expression, we identify a bacterial gene cluster that performs 21-dehydroxylation.We also uncover an unexpected role for hydrogen gas production by gut commensals inpromoting 21-dehydroxylation, suggesting that hydrogen modulates secondary metabolismin the gut. Levels of certain bacterial progestins, including allopregnanolone, betterknown as brexanolone, an FDA-approved drug for postpartum depression, are substantiallyincreased in feces from pregnant humans. Thus, bacterial conversion of corticoidsinto progestins may affect host physiology, particularly in the context of pregnancyand women’s health.
DOI: 10.1016/j.cell.2024.05.005
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00514-2