Other Gut Bacteria Produce Hormone Involved in Postpartum Depression. Study demonstrates how gut microbes process steroids — using flatulence (May 2024) Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas

[Michael Harrop]

https://hms.harvard.edu/news/gut-bacteria-produce-hormone-involved-postpartum-depression
https://www.cell.com/cell/abstract/S0092-8674(24)00514-2

At a glance:

• Study shows two related kinds of gut bacteria can modify steroids differently from how human cells do and demonstrates that gas affects which ones gut bacteria produce.
• Work suggests gut microbiota can act like an endocrine organ, producing hormones that affect human health.
• Findings provide new evidence that doctors could one day treat certain mental health conditions by manipulating the gut microbiome.

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Gas released by some gut bacteria stimulates other gut bacteria to produce a hormone involved in pregnancy and in an FDA-approved treatment for postpartum depression

The work shows how gut bacteria can produce new hormones from steroids in bile and, in doing so, act like an endocrine organ.

“Our cells make steroids only in the oxidative direction, that is, losing electrons, whereas we’ve shown that gut bacteria can go in the reverse direction, known as reduction, or gaining electrons — making the bacterial transformation unique,”

The team found that the bacteria can alter corticoids found in bile — steroids that play roles in immune function and metabolism. The bacteria turn them into progesterone derivatives, which are sex hormones and neurosteroids that affect the brain and nervous system.

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Highlights​

• Gordonibacter and Eggerthella 21-dehydroxylate host corticoids to produce progestins
• Bacterial production of hydrogen gas promotes 21-dehydroxylation
• The 21-dehydroxylation genes were identified using comparative and functional genomics
• Progestin levels and gene cluster abundance were significantly higher during pregnancy

Summary​

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.

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[SFBayFMT5]

Interesting! We've known about bile acid dehydroxylation for decades, the fact that they can do the same at other positions of the steroid nucleus is not a complete surprise, but still this has potential significant consequences given the very different hormonal effects of compounds differing by only a few atoms. By contrast, bile acid transformation, while very significant in terms of protecting the microbiome from bile acid stress, only effectively changes one kind of detergent into another.