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. 2024 Jun 6;187(12):2952-2968.e13.
doi: 10.1016/j.cell.2024.05.005. Epub 2024 May 24.

Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas

Megan D McCurry  1 , Gabriel D D'Agostino  1 , Jasmine T Walsh  1 , Jordan E Bisanz  2 , Ines Zalosnik  3 , Xueyang Dong  4 , David J Morris  5 , Joshua R Korzenik  6 , Andrea G Edlow  7 , Emily P Balskus  8 , Peter J Turnbaugh  9 , Jun R Huh  3 , A Sloan Devlin  10
Affiliations

Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas

Megan D McCurry et al. Cell. .

Abstract

Recent studies suggest that human-associated bacteria interact with host-produced steroids, but the mechanisms and physiological impact of such interactions remain unclear. Here, we show that the human gut bacteria Gordonibacter pamelaeae and Eggerthella lenta convert abundant biliary corticoids into progestins through 21-dehydroxylation, thereby transforming a class of immuno- and metabo-regulatory steroids into a class of sex hormones and neurosteroids. Using comparative genomics, homologous expression, and heterologous expression, we identify a bacterial gene cluster that performs 21-dehydroxylation. We also uncover an unexpected role for hydrogen gas production by gut commensals in promoting 21-dehydroxylation, suggesting that hydrogen modulates secondary metabolism in the gut. Levels of certain bacterial progestins, including allopregnanolone, better known as brexanolone, an FDA-approved drug for postpartum depression, are substantially increased in feces from pregnant humans. Thus, bacterial conversion of corticoids into progestins may affect host physiology, particularly in the context of pregnancy and women's health.

Keywords: 21-dehydroxylation; Eggerthella lenta; hydrogen gas; neurosteroids.

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Conflict of interest statement

Declaration of interests A.S.D. is an ad hoc consultant for Axial Therapeutics. M.D.M. and A.S.D. are co-inventors on a provisional patent related to this work. J.R.H. serves as a consultant for CJ CheilJedang and is a co-founder and consultant for Interon Laboratories. He received research funding from CJ Bioscience outside the submitted work. A.G.E. serves as a consultant for Mirvie, Inc. outside the submitted work and receives research funding from Merck Pharmaceuticals outside the submitted work.

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