Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas.
Cell
; 187(12): 2952-2968.e13, 2024 Jun 06.
Article
en En
| MEDLINE
| ID: mdl-38795705
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Progestinas
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Microbioma Gastrointestinal
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Glucocorticoides
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Hidrógeno
Idioma:
En
Revista:
Cell
Año:
2024
Tipo del documento:
Article