For some time, we’ve known that there’s a complex interplay between hormones, internal organs, and mental health, but disentangling the most relevant connections within the body has proven difficult.
A new study has discovered a single enzyme that connects all three, and its presence may be responsible for depression in women of reproductive age.
Di Li, a medical researcher at Wuhan University, and his colleagues compared sera from 91 women aged 18 to 45 with those from 91 depressed and 98 nondepressed women. Incredibly, serum levels in depressed patients were Estradiol – The primary form of estrogen that our bodies use during fertile periods.
The idea that estradiol is linked to depression in people with fertile female hormones over 100 years oldThe natural decline in estradiol during and after menopause is associated with notorious mood changes.
Polycystic ovary syndrome (which causes the ovaries to produce more than normal levels of sex hormones known as androgens, causing an imbalance in reproductive hormones) and congenital adrenal hyperplasia (which depletes one of the enzymes the body needs). other conditions, including a group of genetic disorders lacking) to make certain hormones), as well as low estradiol and depression.
Association between depression and estradiol explain why It is about twice as common in women than in men.
Estradiol is produced in the ovaries, performs chores around the body including regulating the menstrual cycle, and is then metabolized in the liver before being sent to the intestines. It helps maintain circulating levels of estrogen.
Armed with this knowledge, researchers investigated the activity of estradiol in the gut.
Within 2 hours of adding estradiol to fecal microbiome samples from depressed women, the hormone was degraded by 78%. By contrast, a tube containing a microbiome sample from a non-depressed woman had her hormones reduced by only 20%.
Scientists also transplanted the gut microbiota of five depressed women into mice, which showed a 25% reduction in serum estradiol levels compared to control mice.
It is clear that gut microbes are responsible for increasing the breakdown of this hormone within the digestive system.
To isolate the causative organism, Lee and team placed microbiome samples taken from depressed women on agar plates and provided estradiol as the sole food source. % or more decomposed. estrone.
White blobs with smooth, fuzzy edges flourished, and using mass spectrometry, researchers identified the microbes. Klebsiella aerogenes TS2020.
“These results K. aerogenes TS2020 It can lower serum estradiol levels in mice and induce depression-like behavior,” said the researchers. explain in their paper“Additionally, administration of cefotaxime can alleviate such depressive-like behaviors in mice.”
Genetic analysis showed that K. aerogenes It converts estradiol to estrone with an enzyme called 3β-HSD (3β-hydroxysteroid dehydrogenase).the gene for this enzyme Escherichia coli And when mice were infected with these bacteria, estradiol was similarly lowered and depressive symptoms developed.
Giving control mice estrone did not increase depressive behavior, suggesting that excess estrone was not the problem.Li and colleagues ruled out other molecules as well.
3β-HSD producing mouse Escherichia coli They also had lower estradiol levels in the brain, including the hippocampus. deeply involved in depressionTaken together, all this suggests that enzymes produced by microbes are causing brain problems.
and previous research, researchers found elevated levels of the same enzyme in male patients with depression. This enzyme also breaks down testosterone.
“Taking together these two studies, we speculate that the 3β-HSD enzyme is involved in the development of depression, and that this relationship is gender-independent,” said the researchers. explanation.
“We believe that K. aerogenes It is not the only intestinal bacterium capable of producing 3β-HSD in feces. Our metagenomic sequencing data are Bacteroides thetaiotaomicron and Clostridium Bacteria have 3β-HSD. However, it is possible that there are other His 3β-HSD-producing enterobacteria below the detection limit of metagenomic sequencing. Further research is needed to determine which bacteria can produce her 3β-HSD. ”
Estrogen replacement therapy is gaining attention as a treatment for depression in women, and if the pathway identified here proves accurate, 3β-HSD-producing bacteria could lead to relapse. , warns Li and the team.
“The estradiol-degrading bacteria in the gut, particularly the enzymes expressed by these bacteria, may be better targets for intervention. Note.
almost 280 million people I suffer from depression all over the world. For those of us who rely on outside help for our brain chemistry, better treatment options to come from understanding these brain-gut-hormonal connections won’t appear anytime soon.
This research cell metabolism.
