Gut Bacteria Improve Depressive Symptoms by Degrading Cortisol into Androgen.

Gut microbiota has a heterogeneous ability to degrade cortisol among individuals.

• The study found that gut microbiota degraded cortisol, but this ability varied across individuals.
• Mice gavaged with gut microbiota having a low ability to degrade cortisol were prone to developing depressive-like behavior.
• This heterogeneity in cortisol-degrading capacity was a central finding linking gut microbiota composition to stress hormone regulation.

Pseudomonas aeruginosa Tongji was isolated from fecal microbiota as a cortisol-degrading strain.

• The strain P. aeruginosa Tongji was specifically isolated from fecal microbiota based on its cortisol-degrading ability.
• This strain expresses a des-like enzyme responsible for the conversion of cortisol.
• The isolation identified P. aeruginosa Tongji as a functionally relevant member of the gut microbiota with respect to cortisol metabolism.

The des-like enzyme expressed by P. aeruginosa Tongji converts cortisol into androgen.

• The des-like enzyme was identified as the specific enzymatic mechanism by which P. aeruginosa Tongji degrades cortisol.
• The enzymatic product of cortisol degradation was identified as androgen.
• This conversion represents a novel bacterial steroid-metabolizing pathway relevant to host physiology.

Bacterial des-like enzyme protected mice against depressive-like behavior through cortisol degradation and androgen production.

• Administration of the des-like enzyme protected mice from developing depressive-like behavior.
• The protective effect was attributed to both the reduction of cortisol and the production of androgen.
• These findings suggest a dual mechanism—stress hormone reduction and androgenic signaling—underlying the antidepressant effect.

A recombinant probiotic Bacillus subtilis expressing the des-like enzyme was engineered and protected the host against cortisol elevation.

• The authors constructed a probiotic strain of Bacillus subtilis that heterologously expressed the des-like enzyme.
• This engineered probiotic protected the host against cortisol elevation in experimental models.
• The use of B. subtilis as a delivery vehicle represents a translational approach to modulating cortisol via the gut microbiome.

Gut microbiota may regulate the stress hormone cortisol, but the underlying mechanisms were previously poorly understood.

• The paper states that 'gut microbiota may play a role in regulating the stress hormone cortisol.'
• 'The mechanisms underlying the regulation of cortisol by gut microbiota are poorly understood' prior to this study.
• This study aimed to fill that mechanistic gap by identifying a specific bacterial enzyme and metabolic pathway.