2024 · McCurry — Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas.
Super-Abstract
Two common gut bacteria can chemically transform stress hormones (glucocorticoids) into sex hormones and neurosteroids (progestins) — and this conversion is significantly boosted by hydrogen gas produced by other gut bacteria. The bacterial progestins include allopregnanolone (the active ingredient in an FDA-approved postpartum depression drug), and their levels are elevated in feces from pregnant humans. (Cell, 2024.)
Commentary
This is a high-impact mechanistic study published in Cell. The authors discovered that Gordonibacter pamelaeae and Eggerthella lenta — both common gut commensals — convert biliary corticoids (bile-derived glucocorticoids such as deoxycholic acid derivatives) into progestins through a reaction called 21-dehydroxylation. Using comparative genomics, homologous expression, and heterologous expression in E. coli, they identified the specific gene cluster responsible. Crucially, they found that hydrogen gas produced by other gut bacteria acts as a co-factor that dramatically enhances this conversion — the H₂ here is endogenously produced by gut microbiota, not consumed as therapy. Levels of allopregnanolone — an FDA-approved drug for postpartum depression (brexanolone) — were substantially elevated in feces from pregnant humans. This suggests that gut bacteria may influence hormone levels and mood, particularly during pregnancy, via H₂-dependent secondary metabolism. This is a landmark mechanistic finding, but the therapeutic or clinical implications remain to be worked out.
Key quotes
- „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.“ — the core discovery: gut bacteria can remodel the body's steroid hormone landscape
- „we uncover an unexpected role for hydrogen gas production by gut commensals in promoting 21-dehydroxylation, suggesting that hydrogen modulates secondary metabolism in the gut.“ — the key H₂ finding: endogenous gut H₂ acts as a metabolic regulator — not as an exogenous therapy
- „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.“ — the physiological relevance: bacterial hormone production may matter especially during pregnancy
Our assessment
This is an in-vitro mechanistic study (bacterial cultures, genomics, cell expression systems) with supporting observational human fecal data. It is a landmark paper in gut microbiome research, published in Cell, revealing a completely new dimension of how gut bacteria interact with host steroid metabolism. The H₂ involved is endogenous microbial H₂ — not an exogenous H₂ therapy. While the findings have profound implications for understanding the gut-brain axis and pregnancy physiology, no intervention or treatment is studied. The clinical implications (e.g., can modulating gut H₂ producers affect hormone levels or depression risk?) remain entirely speculative at this stage.
Study design
- Type: in-vitro microbiology + comparative genomics + observational human fecal analysis · Model: Gordonibacter/Eggerthella cultures, E. coli heterologous expression, pregnant human fecal samples · H₂ role: endogenous gut microbiota H₂ production enhances steroid 21-dehydroxylation
- Result: gene cluster for 21-dehydroxylation identified; gut H₂ promotes corticoid-to-progestin conversion; allopregnanolone elevated in pregnant human feces — mechanistic, no intervention tested in humans or animals
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.
Source & links
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