Mood disorders are increasingly recognized as systemic conditions involving immune dysregulation and gut–brain axis disturbances. While probiotics and prebiotics have been extensively studied, the mechanistic and therapeutic roles of postbiotics—the bioactive metabolites produced by microorganisms—remain insufficiently synthesized in psychiatric research. This review addresses this gap by examining how key postbiotic compounds, including short-chain fatty acids (SCFAs), gamma-aminobutyric acid (GABA), serotonin, dopamine, tryptophan metabolites, and oxytocin, modulate neuroimmune pathways implicated in depression and related disorders. Mechanistically, postbiotics influence histone deacetylase activity, G-protein–coupled receptor signaling, cytokine production, microglial activation, and blood–brain barrier integrity. Emerging clinical data suggest adjunctive benefits in stress, anxiety, and depressive symptoms, though dose-response relationships and long-term outcomes remain underexplored. Overall, postbiotics represent a promising mechanistically targeted strategy for modulating the gut–brain–immune axis; however, rigorous clinical trials are required to validate therapeutic efficacy and optimize formulation and dosing strategies.
Homayouni-Rad et al. (Wed,) studied this question.
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