Summary: Researchers have discovered that gut bacteria produce a hormone involved in treating pregnancy and postpartum depression by modifying steroids found in bile. This research highlights the role of the microbiome as an endocrine organ influencing human health.
The results suggest that gut bacteria could be targeted to treat mental health problems. The study opens new avenues for understanding gut-brain interactions.
Highlights:
- Hormone production: Gut bacteria produce allopregnanolone, a hormone linked to pregnancy and mood regulation.
- The role of the microbiome: The microbiome acts as an endocrine organ, influencing human health and behavior.
- Potential therapies: Research suggests that targeting gut bacteria could help treat mental health issues like postpartum depression.
Source: Harvard
It turns out that flatulence can serve more than just being uncomfortable or fun: Gases released by some gut bacteria stimulate other gut bacteria to produce a hormone involved in pregnancy and an FDA-approved treatment for postpartum depression, according to new research from Harvard Medical. School scientists.
The work shows how gut bacteria can produce new hormones from steroids in bile and, in doing so, act as an endocrine organ. This research adds to the growing list of ways the gut microbiota can influence human biology and health.
The study also provides new evidence that doctors could one day treat or prevent certain types of mental health problems by manipulating the gut microbiome.
The results are published on May 24 in Cell.
“While it is common knowledge that gut health is important to our overall well-being, the exact way in which the bacteria that reside in our digestive tract interact with each other and with our own cells to impact our mental health is still being discovered,” said first author Megan. McCurry, who conducted the work as a graduate student and postdoctoral researcher in the lab of Sloan Devlin at the Blavatnik Institute at HMS.
“This work reveals how certain gut bacteria carry out a chemical transformation that produces a steroid that may impact women’s health and postpartum depression.”
Insects that make drugs
Working in laboratory dishes and with mice, McCurry and his colleagues discovered two types of related bacteria in the human gastrointestinal tract: Gordonibacter pamelaeae And Eggerthella lenta – which can modify steroids. They further discovered that this chemical change occurs in the opposite direction to the way human cells make steroids.
“Our cells make steroids only in the oxidative direction, that is, by losing electrons, whereas we have shown that gut bacteria can go in the opposite direction, called reduction, or gain electrons, which makes bacterial transformation unique,” Devlin said.
The team found that the bacteria can modify corticosteroids found in bile, steroids that play a role in immune function and metabolism. Bacteria convert them into progesterone derivatives, which are sex hormones and neurosteroids that affect the brain and nervous system.
“We know that the human body produces progesterone in the adrenal glands, placenta and ovaries. Our work suggests that the microbiome acts as an additional endocrine organ,” said Devlin, HMS associate professor of biological chemistry and molecular pharmacology and senior author of the study.
Devlin and his team discovered that one of the progesterone derivatives produced by gut bacteria is allopregnanolone, so named a century ago because the body produces it during pregnancy.
In partnership with Andrea Edlow, HMS associate professor of obstetrics, gynecology and reproductive biology at Massachusetts General Hospital, the team studied allopregnanolone production during pregnancy.
Analysis of fecal samples from study participants revealed that women in the third trimester of pregnancy not only had 100 times higher levels of allopregnanolone, but also more genetic traces of both gut bacteria than people without. speakers.
The results suggest that gut bacteria contribute to the production of allopregnanolone during pregnancy.
Researchers have linked low levels of allopregnanolone to postpartum depression and other mood and psychiatric disorders, and allopregnanolone is used as an FDA-approved drug, known as brexanolone, to treat postpartum depression.
With that in mind, Devlin and colleagues want to expand their study using fecal samples to follow participants during the first, second, and third trimesters and after delivery and see who develops postpartum depression.
The goal is to better understand whether gut bacteria contribute to allopregnanolone levels throughout pregnancy and increase the risk of or protect against postpartum depression.
If researchers find an effect, “in the future, as a community, we might think about microbiome-targeted therapies for neurological diseases like depression,” Devlin said.
Behind the chemistry
The researchers also revealed how the two bacteria carry out their chemical transformations.
First, they identified the genes at work. Second, they found that the G. pamelea And E. lenta Bacteria need hydrogen – one of the gases that other bacteria in our gastrointestinal tract produce when they digest food.
“The effects of gases on bacterial metabolism have been largely neglected, probably because studying them in the laboratory is very difficult,” she said. “Our work suggests that there are likely other intestinal bacterial processes that are primarily affected by flatulence.”
The team hopes this work will demonstrate that chemistry driven by gut bacteria impacts human health and behavior, in this case during pregnancy.
“Before our work, the prevailing view was that the host was manufacturing steroids; the microbiome was not part of the conversation,” Devlin said.
“We hope this work will convince people that gut bacteria modify steroids to produce molecules that can affect host functions, including mood and behavior.”
Funding:
McCurry is now a scientist at the biotechnology company Holobiome. Other authors are Gabriel D’Agostino and Jasmine Walsh, both doctoral students in chemical biology at the Harvard Kenneth C. Griffin Graduate School of Arts and Sciences studying in the Devlin lab, as well as Jordan E. Bisanz, Ines Zalosnik, Xueyang Dong, David . J. Morris, Joshua R. Korzenik, Emily Balskus, Peter J. Turnbaugh and Jun R. Huh, associate professor of immunology in the Blavatnik Institute at HMS.
The study was supported by the National Institutes of Health (grants R35GM128618, R01DK110559, R01HL122593, R01HD100022), an Alfred P. Sloan Fellowship, the Simons Foundation (SFARI grant 870754), the National Science Foundation (Alan T. Waterman CHE Award -20380529) and the Resnek Family Center for Primary Sclerosing Cholangitis Research.
McCurry was funded by an NSF Graduate Research Fellowship (No. DGE1745303), an HMS Christopher T. Walsh Graduate Fellowship, an HMS Graduate Program in Bacteriology NIH T32 Grant, and a HMS BCMP Van Maanen. Balskus is a Howard Hughes Medical Institute investigator. Proteomic analyzes were performed at the HMS BCMP MassSpec Center, and imaging, consultation, and SEM services were performed at the HMS main electron microscopy facility.
Devlin is an ad hoc consultant for Axial Therapeutics. McCurry and Devlin are co-inventors on a provisional patent related to this work. Huh is a consultant for CJ CheilJedang and co-founder and consultant for Interon Laboratories. He has received research funding from CJ Bioscience outside the submitted work. Edlow serves as a consultant for Mirvie, Inc., outside the submitted work and receives research funding from Merck & Co., Inc., outside the submitted work. All other authors declare no competing interests.
About this news on microbiome research, pregnancy and PPD
Author: Stephanie Dutchen
Source: Harvard
Contact: STEPHANIE DUTCHEN – Harvard
Picture: Image is credited to Neuroscience News
Original research: Closed access.
“Gut bacteria convert glucocorticoids to progestins in the presence of hydrogen gas” by Megan McCurry et al. Cell
Abstract
Gut bacteria convert glucocorticoids to progestins in the presence of hydrogen gas
Strong points
- Gordonibacteria And Eggerthella 21-dehydroxylated host corticosteroids to produce progestins
- Bacterial production of hydrogen gas promotes 21-dehydroxylation
- 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 these interactions remain unclear.
Here we show that human gut bacteria Gordonibacter pamelaeae And Eggerthella lenta convert abundant biliary corticosteroids to progestins by 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 medication for postpartum depression, are significantly increased in the stools of pregnant women.
Thus, bacterial conversion of corticosteroids to progestins may affect host physiology, particularly in the context of pregnancy and women’s health.
News Source : neurosciencenews.com
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