Postpartum: Gut Bacteria May Ease Depression

Summary: By altering steroids in bile, gut bacteria have been shown to make a hormone that is implicated in pregnancy and the treatment of postpartum depression. This study emphasizes how the microbiome functions as an endocrine organ that affects human health.

Findings imply that treating mental health issues may involve targeting gut flora. The findings pave new paths in our knowledge of gut-brain communication.

Important Details:

Production of Hormones: Allopregnanolone, a hormone associated with mood control and pregnancy, is produced by gut bacteria.

The role of the microbiome is that it influences human behavior and health by functioning as an endocrine organ.

Potential Therapies: Studies indicate that treating mental health issues including postpartum depression may benefit from focusing on gut bacteria.

Harvard is the source

It turns out that flatulence has uses other than being amusing or uncomfortable: According to recent research headed by experts at Harvard Medical School, gas emitted by certain gut bacteria stimulates other gut bacteria to create a hormone implicated in pregnancy and in an FDA-approved treatment for postpartum depression.

The research demonstrates how gut bacteria can function as an endocrine organ by converting steroids in bile into new hormones. This study broadens our understanding of the potential effects of gut microbiota on human biology and health.

Additionally, the study offers fresh proof that clinicians may use gut microbiome manipulation to treat or prevent certain mental health issues in the future.

The results appear in Cell.

“While it’s common knowledge that gut health is important to our overall well-being, exactly how bacteria that reside in our GI tract interact with one another and with our own cells to impact our mental health is still being uncovered,” First author Megan McCurry, who worked in Sloan Devlin’s lab at the Blavatnik Institute at HMS as a graduate student and postdoctoral research fellow, stated as much.

“This work reveals how certain gut bacteria perform a chemical transformation that produces a steroid that could impact women’s health and postpartum depression.”

Bugs that produce medicines

Gordonibacter pamelaeae and Eggerthella lenta are two related species of bacteria that McCurry and colleagues discovered in the human gastrointestinal tract that can alter steroids. They conducted their research in lab dishes and on mice. They also discovered that the path of this chemical alteration differs from the way human cells produce steroids.

“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,” said Devlin.

The researchers discovered that the bacteria can change the corticoids, or steroids, that are present in bile and are involved in metabolism and immune response. The bacteria convert them into neurosteroids and sex hormones called progesterone derivatives, which have an impact on the nervous system and brain.

“We know that the human body makes 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 colleagues discovered that allopregnanolone, which was called a century ago because the body produces it during pregnancy, is one of the progesterone derivatives that gut bacteria create.

The scientists looked into the production of allopregnanolone during pregnancy in collaboration with Andrea Edlow, an HMS associate professor of obstetrics, gynecology, and reproductive biology at Massachusetts General Hospital.

Study participants’ fecal samples were analyzed, and the results showed that pregnant women in their third trimester not only had 100 times more levels of allopregnanolone than non-pregnant persons but also had more genetic evidence of the two gut bacteria.

The results imply that the synthesis of allopregnanolone during pregnancy is influenced by gut microbes.

Allopregnanolone is used as an FDA-approved medication known as brexanolone to treat postpartum depression. Researchers have connected low levels of allopregnanolone to mood and psychiatric disorders, including postpartum depression.

To find out who gets postpartum depression, Devlin and colleagues aim to extend their fecal sample study to follow people during the first, second, and third trimesters as well as after delivery.

The objective is to obtain further insight into the potential role of gut bacteria in regulating allopregnanolone levels during pregnancy, as well as their potential to either prevent or mitigate postpartum depression. 

If the researchers find an effect, “down the road, as a community, we could think about microbiome-targeted therapies for neurological conditions like depression,” said Devlin.

The chemistry behind it

The two bacteria’s methods for performing chemical changes were also disclosed by the researchers.

They first determined which genes were active. Second, they discovered that hydrogen, one of the gasses other bacteria in our GI tract make when they break down food, is necessary for the G. pamelaeae and E. lenta bacteria.

“The effects of gas on bacterial metabolism have been largely overlooked, likely because studying it in the lab is very difficult,” she said. “Our work suggests that there are likely to be other gut bacterial processes that are significantly affected by, basically, flatulence.”

The research team expects that the findings show how gut chemistry, in this case during pregnancy, affects human behavior and health.

“Before our work, the prevailing understanding was that the host makes steroids; the microbiome was not a part of the conversation,” said Devlin.

“We hope this work convinces people that gut bacteria modify steroids to produce molecules that can affect host functions, including mood and behavior.”

For more information: Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas, Cell, DOI:https://doi.org/10.1016/j.cell.2024.05.005