Gut Bacteria Improve Depressive Symptoms by Degrading Cortisol into Androgen.

Summary

This mechanistic study identifies a bacterial des-like enzyme that converts cortisol to androgen, mitigating depressive-like behavior in mice. An engineered Bacillus subtilis expressing the enzyme blunted cortisol elevation, highlighting a potential microbiome-based therapeutic approach.

Key Findings

• Gut microbiota exhibit heterogeneous capacity to degrade cortisol across individuals.
• Pseudomonas aeruginosa Tongji expresses a des-like enzyme that converts cortisol to androgen.
• Mice receiving low cortisol-degrading microbiota show depressive-like behavior; enzymatic conversion protects against this behavior.
• Engineered Bacillus subtilis expressing the des-like enzyme prevents cortisol elevation in hosts.

Clinical Implications

While preclinical, this work supports developing engineered probiotics or enzyme therapies to modulate cortisol and mood; human safety (androgenic effects) and efficacy must be rigorously tested.

Limitations

• Preclinical animal models without human clinical validation.
• Potential safety concerns due to androgen production and off-target endocrine effects.

Future Directions

Conduct first-in-human safety and pharmacodynamic studies of enzyme/probiotic approaches; map prevalence of cortisol-to-androgen conversion capacity in human microbiomes and its association with depressive phenotypes.