Gut-microbiome-expressed 3β-hydroxysteroid dehydrogenase degrades estradiol and is linked to depression in premenopausal females

Estradiol decline can result in depressive disorders in females; nevertheless, the causes of this decline are unclear. In this study, we isolated estradiol-degrading Klebsiella aerogenes from the feces of premenopausal females with depression. In mice, gavaging with this strain led to estradiol decline and depression-like behaviors. The gene encoding the estradiol-degrading enzyme in K. aerogenes was identified as 3β-hydroxysteroid dehydrogenase (3β-HSD). Heterologously expressing 3β-HSD resulted in Escherichia coli obtaining the ability to degrade estradiol. Gavaging mice with 3β-HSD-expressing E. coli decreased their serum estradiol levels, causing depression-like behaviors. The prevalence of K. aerogene and 3β-HSD was higher in premenopausal women with depression than in those without depression. These results suggest that the estradiol-degrading bacteria and 3β-HSD enzymes are potential intervention targets for depression treatment in premenopausal women.