What is already known
Depression is about twice as common in women as it is in men, likely due to changes in the levels of estradiol, the major female sex hormone. In rodents, low blood estradiol levels induce depression-like behaviors and some studies have linked declining estradiol levels in premenopausal women with depression. However, the causes of this reduction are unclear.
What this research adds
Researchers analyzed estradiol levels and gut microbes from premenopausal women with and without depression. From the stool of premenopausal women with depression, the researchers isolated a strain of Klebsiella aerogenes that is able to degrade estradiol.
Transferring this bacterial strain to the gut of mice led to a decline in estradiol levels and depression-like behaviors. The researchers also identified the gene encoding the estradiol-degrading enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD) in K. aerogenes. The prevalence of K. aerogenes and 3β-HSD was higher in premenopausal women with depression than in those without depression.
Conclusions
The findings suggest that estradiol-degrading bacteria could be therapeutic targets for treating depression in some women.
Women are nearly twice as likely as men to be diagnosed with depression. Now, researchers have found that a species of gut bacteria that can degrade the sex hormone estradiol is associated with depression in premenopausal women.
The findings, published in Cell Metabolism, suggest that estradiol-degrading bacteria could be therapeutic targets for treating depression in some women.
The higher prevalence of depression in women is likely due to changes in the levels of estradiol, the major female sex hormone. In rodents, low blood estradiol levels induce depression-like behaviors and some studies have linked declining estradiol levels in premenopausal women with depression. However, the causes of this reduction are unclear.
Since gut microbes can alter the blood levels of steroid hormones such as estradiol, researchers led by Zhongchun Liu, Gaohua Wang and Yan Li at Renmin Hospital of Wuhan University set out to explore whether the guts of women with depression harbor estradiol-degrading microbes and whether these microbes are linked to depression.
Estradiol-degrading bacteria
The researchers assessed the serum levels of estradiol in 91 premenopausal women with depression and 98 premenopausal women without depression. Women with the condition had lower serum estradiol levels than those without it, and their gut microbiota degraded estradiol more efficiently than that of non-depressed women.
Mice receiving fecal transplants from depressed premenopausal women showed depression-like behaviors and had lower estradiol blood levels than control mice, the researchers found.
From the stool of premenopausal women with depression, the team isolated a strain of Klebsiella aerogenes that is able to break down estradiol. Transferring this bacterial strain to the gut of mice led to a decline of estradiol levels and depression-like behaviors.
Therapeutic targets
Using whole genome sequencing, the researchers were able to identify the gene encoding the estradiol-degrading enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD) in K. aerogenes. What’s more, they observed that the prevalence of K. aerogenes and 3β-HSD was higher in premenopausal women with depression than in those without depression.
Mice colonized with Escherichia coli bacteria expressing 3β-HSD had decreased serum estradiol levels. The animals also showed depression-like behaviors, which were eased by estradiol supplementation, the researchers found.
“It is worth noting that, even though estradiol supplementation improved depression-like behaviors in mice in this study, active bacteria in the mouse gut expressing the 3β-HSD enzyme could cause depression relapse,” the researchers say. “Therefore, estradiol-degrading bacteria in the gut, particularly the enzymes expressed by these bacteria, may be better targets for intervention.”
