Probiotics as a Tool for Regulating Molecular Mechanisms in Depression: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Depression is one of the main mental disorders. Pharmacological treatment is often associated with delayed effects or insufficient efficacy, creating a need for new therapeutic options. Evidence suggests probiotic therapy can reduce depressive symptoms, but mechanisms linking gut microbiota to the CNS and probiotics’ modes of action remain unclear. This PRISMA-based systematic review and meta-analysis summarized molecular mechanisms in healthy populations with subclinical depression/anxiety and in depressed patients with or without somatic comorbidities. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated. Twenty records were included. Probiotic administration was linked to a significant increase in BDNF levels versus placebo (SMD = 0.37, 95% CI [0.07, 0.68], p = 0.02) in depressed patients with or without somatic comorbidities. Among depressed patients with somatic comorbidities, CRP levels were significantly lower (SMD = −0.47, 95% CI [−0.75, −0.19], p = 0.001) and nitric oxide levels were significantly higher (SMD = 0.97, 95% CI [0.58, 1.36], p < 0.0001) with probiotics. No significant differences were found for IL-1β, IL-6, IL-10, TNF-α, or cortisol (all p > 0.05). Firm conclusions on probiotic effectiveness and associations with inflammatory markers in healthy populations with subclinical symptoms cannot be drawn. Long-term clinical trials are needed to evaluate durability and preventive potential of probiotic effects in depression.