Gut Bacteria Improve Depressive Symptoms by Degrading Cortisol into Androgen

Abstract Gut microbiota may play a role in regulating the stress hormone cortisol. However, the mechanisms underlying the regulation of cortisol by gut microbiota are poorly understood. Here, it is found that gut microbiota degraded cortisol, and this ability is heterogeneous among individuals. Mice gavaged with gut microbiota having a low ability to degrade cortisol may be prone to developing depressive‐like behavior. The cortisol‐degrading strain Pseudomonas aeruginosa Tongji is isolated from faecal microbiota. The des‐like enzyme expressed by P. aeruginosa Tongji converts cortisol into androgen. Bacterial des‐like enzyme protects mice against depressive‐like behavior via degrading cortisol and producing androgen. The probiotic Bacillus subtilis expressing the des‐like enzyme is constructed, which protects the host against cortisol elevation. These findings suggest that bacterial des‐like enzyme may regulate cortisol and improve depression by converting cortisol into androgen.