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

Di Li, Ran Liu, Ming Wang, Rui Peng, Shuai Fu, Aisi Fu, Juan Le, Qian Yao, Tengfei Yuan, Haoming Chi, Xin Mu, Ting Sun, Hang Liu, Pan Yan, Shaoting Wang, Shu Cheng, Zixin Deng, Zhongchun Liu, Gaohua Wang, YanLi, TiangangLiu

Cell Host & Microbe Volume 30, Issue 3, 9 March 2022, Pages 329-339.e5

https://doi.org/10.1016/j.chom.2022.01.001

Abstract

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 3β-hydroxysteroid dehydrogenase (3β-HSD) as the enzyme causing testosterone degradation. Introducing 3β-HSD into Escherichia coli enhanced its ability to degrade testosterone. Gavaging rats with 3β-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 3β-HSD, and 60.87% (28/46) of these fecal samples expressed 3β-HSD. These results suggest that 3β-HSD expressed by gut microbes may be associated with depressive symptoms due to testosterone degradation.