Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas
Megan D. McCurry; Gabriel D. D'Agostino; Jasmine T. Walsh; Jordan E. Bisanz; María Inés Zalosnik; Xueyang Dong; David J. Morris; Joshua R. Korzenik; Andrea G. Edlow; Emily P. Balskus; Peter James Turnbaugh; Jun R. Huh; A. Sloan Devlin
Cell2024
Summary (paraphrased)
Two human gut bacteria, Gordonibacter pamelaeae and Eggerthella lenta, were found to convert abundant biliary corticoids into progestins via 21-dehydroxylation — the chemical reverse of how human cells make steroids. The responsible bacterial gene cluster was identified by comparative and functional genomics, and commensal hydrogen-gas production was shown to promote the reaction. In pregnant human fecal samples, levels of bacterial progestins including allopregnanolone were substantially elevated. The authors propose the microbiome functions as an additional endocrine organ interconverting steroid classes.
Why it’s in the systems review
This is the strongest primary-data paper for the microbiome–neurosteroid link in the corpus: gut bacteria were shown to manufacture allopregnanolone, the same neurosteroid the Melcangi group has repeatedly implicated in finasteride's long-term CNS effects. It reframes the gut not merely as a steroid recycler but as a net producer of neuroactive steroids, which belongs in both the causal-pathway search (a second neurosteroid source that finasteride withdrawal might perturb) and the treatment-candidate landscape.
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