3β-Hydroxysteroid dehydrogenase expressed by gut microbes degrades testosterone and is linked to depression in males

Testosterone deficiency can lead to depressive symptoms in humans; however, the causes of this deficiency are incompletely understood. Here, we isolated Mycobacterium neoaurum from the fecal samples of testosterone-deficient patients with depression and showed that this strain could degrade testosterone in vitro. Furthermore, gavaging rats with M. neoaurum reduced their serum and brain testosterone levels and induced depression-like behaviors. We identified the gene encoding 38-hydroxysteroid dehydrogenase (3 beta-HSD) as the enzyme causing testosterone degradation. Introducing 3 beta-HSD into Escherichia coli enhanced its ability to degrade testosterone. Gavaging rats with 3 beta-HSD-producing E. coli reduced their serum and brain testosterone levels and caused depression-like behaviors. Finally, compared with 16.67% of participants without depression, 42.99% (46/107) of the fecal samples of patients with depression harbored 3 beta-HSD, and 60.87% (28/46) of these fecal samples expressed 3 beta-HSD. These results suggest that 3 beta-HSD expressed by gut microbes may be associated with depressive symptoms due to testosterone degradation.

Automated summary

Testosterone deficiency can lead to depressive symptoms, and gut microbes expressing 3β-HSD may be associated with depressive symptoms caused by testosterone degradation.