We’ve known for some time that there is a complex interplay between our hormones, our bodies and our mental health, but sorting out the connections deeper within our bodies has proven to be a challenge.
New investigations have found a single enzyme that links the three parts, and its presence may be responsible for depression in women.
Di Li, a researcher at Wuhan University, and colleagues compared the blood of 91 women with depression, aged between 18 and 45, and 98 without depression. Those who were depressed had almost half of estradiol levels – the main form of estrogen that the body produces during the fertile years.
The idea that estradiol is linked to depression is over 100 years old. The natural declines in estradiol during menopause and after pregnancy are notoriously linked to mood swings, reported the Science Alert.
Other conditions, including polycystic ovary syndrome and congenital adrenal hyperplasia, can also lead to low estradiol and depression. The estradiol link of depression explains why it is about twice as common in women as in men.
Produced in the ovaries, the estradiol is metabolized in the liver and then passes into the intestine. Here, the hormone is partially reabsorbed back into the bloodstream to help maintain circulating estrogen levels. With this knowledge, the investigators investigated the activities of estradiol in the gut.
Two hours after adding estradiol to fecal microbiological samples from women with depression, there was a 78% breakdown in the hormone. However, the tube with microbiological samples from the women without depression experienced only a 20% decline in the hormone.
The scientists also transplanted the gut microbiota of 5 of the women with depression into mice, which showed a 25% decrease in estradiol levels in the blood compared to the control group. The intestinal microbiota is responsible for the increased degradation of this hormone in the digestive system.
To isolate the microbe responsible, Li and the team placed samples of the depressed women’s microbiome on an agar plate and provided them with estradiol as their only dietary source. Two hours later, more than 60% of the estradiol had been degraded into estrone.
The researchers identified the microbe, a strain of bacteria they labeled Klebsiella aerogenes TS2020.
“These results show that the K. aerogenes TS2020 can reduce estradiol level in rats and induce depressive behaviors”explained the researchers in the study, published in Cell Metabolism. “Furthermore, administration of cefotaxime can alleviate such depressive behaviors in rats.”
Gene analysis showed that the K. aerogenes converts estradiol to estrone with an enzyme called 3β-HSD (3β-hydroxysteroid dehydrogenase). Placing the gene for this enzyme in E. coli and then infecting mice with these bacteria led to the same loss of estradiol and the onset of depressive symptoms.
Giving control estrone to the rats did not increase depressive behavior, ruling out excess estrone as the problem.
Mice with 3β-HSD producing E. coli also had lower levels of estradiol in the brain, including in the hippocampus, a brain region known to be involved in depression. Taken together, this all suggests that the enzyme produced by the microbes is causing the problems.
In a previous study, researchers identified increased levels of the same enzyme in male patients with depression – the enzyme can also degrade testosterone.
“Taking these two studies together, we speculate that the 3β-HSD enzyme is involved in the development of depression and that this relationship is independent of gender,” the researchers wrote.
“We believe that the K. aerogenes in faeces is not the only intestinal bacteria that can produce 3β-HSD. Our metagenomic sequencing data showed that bacteria thetaiotaomicron Bacteroides It is Clostridia have 3β-HSD. However, there may be other 3β-HSD producing gut bacteria below the detection limit of metagenomic sequencing,” they report.
There has been some focus on estrogen replacement therapy as a possible treatment for depression in women, but if the pathway discovered here turns out to be accurate, the 3β-HSD-producing bacteria could lead to relapses.
“The bacteria that break down estradiol in the gut, particularly the enzymes expressed by these bacteria, may be better targets for intervention,” the team noted.
About 280 million people suffer from depression all around the world.
ZAP // 
