Microbial metabolites in the gut-brain axis: their impact on depression pathophysiology and treatment

A review screened 1,249 records and included 23 studies on gut microbial metabolites related to major depressive disorder (MDD).

• Tryptophan metabolism impacts serotonin and kynurenine pathways, contributing to neuroinflammation and neurotransmitter imbalance.
• Short-chain fatty acids (SCFAs), particularly butyrate, act as histone deacetylase inhibitors, influencing gene expression and neuroinflammation.
• GABA-producing bacteria may enhance synaptic plasticity and reduce hyperactivity of the hypothalamic-pituitary-adrenal axis.
• Other metabolites, such as homovanillic acid and β-hydroxybutyrate, are associated with neuroprotective effects and neurotransmitter dynamics.
• Microbiome-modifying interventions, including probiotics and dietary changes, show promise in animal models for addressing metabolite dysregulation and improving depressive symptoms.

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