Major depressive disorder (MDD) causes a substantial global health burden, yet current pharmacological and psychotherapeutic treatments often yield delayed or incomplete relief and carry undesirable side effects. Research on the gut brain axis describes a bidirectional network in which microbial metabolites modulate limbic regions via vagal pathways, intestinal barrier disruption and endotoxin induced inflammation activate systemic and central immune responses, and shifts in tryptophan metabolism reduce serotonin precursor availability while generating neurotoxic compounds. Clinical and preclinical studies suggest that probiotic supplementation can alleviate depressive symptoms and restore key biomarkers of neuroplasticity and inflammation, sometimes in combination with standard antidepressant regimens. However, variability in strain efficacy and host responses poses challenges for clinical translation. Future investigations leveraging large scale multiomics profiling, real time microbiome monitoring and artificial intelligence driven patient stratification will be essential to develop precision microbial interventions and integrate them into comprehensive depression treatment strategies. This review evaluates the mechanistic links between gut microbiota dysbiosis and depression and synthesizes current evidence for probiotics as adjunctive therapy.
Yifan Wang (Wed,) studied this question.