# Gut Bacteria Improve Depressive Symptoms by Degrading Cortisol into Androgen

## TL;DR

Gut bacteria can reduce stress by converting cortisol into androgen, potentially improving depression.

## Contribution

Discovery of a bacterial enzyme that degrades cortisol into androgen, offering a novel approach to treating depression.

## Key findings

- Gut microbiota with low cortisol-degrading ability may lead to depressive-like behavior in mice.
- Pseudomonas aeruginosa Tongji converts cortisol into androgen via a des-like enzyme.
- A probiotic expressing the cortisol-degrading enzyme protects against cortisol elevation and depressive symptoms.

## 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.

Chronic stress is an important risk factor for stress‐related disorders such as depression. Stress hormone cortisol is essential for the pathogenesis of stress‐related disorders such as depression. Some gut microbiota degraded cortisol, and improve depressive symptoms. Probiotic expressing the cortisol‐degrading enzyme protected host against cortisol elevation is an effective intervention measure for depression.