Efficacy of Probiotics in Reducing Depressive Symptoms: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Emerging evidence suggests that the gut–brain axis plays a significant role in the pathophysiology of depression, highlighting probiotics as a potential therapeutic intervention. However, findings from randomized controlled trials (RCTs) remain inconsistent.

Objective: To evaluate the efficacy of probiotic supplementation in reducing depressive symptoms through a systematic review and meta-analysis of randomized controlled trials.

Methods: A comprehensive literature search was conducted in PubMed/MEDLINE and Google Scholar and randomized controlled trials published in last 10 years assessing the effects of probiotics on depressive symptoms in human participants were included. Data were extracted independently by two reviewers. The primary outcome was change in depressive symptoms at end of treatment, measured using validated scales. A random-effects model was used to calculate pooled standardized mean differences (Hedges’ g) with 95% confidence intervals (CI). Subgroup analyses were performed based on baseline depression severity and intervention duration.

Results: Fifteen RCTs involving 1,066 participants were included. Probiotic supplementation was associated with a statistically significant reduction in depressive symptoms compared with placebo (Hedges’ g = −0.50; 95% CI: −0.86 to −0.15; p = 0.005), with substantial heterogeneity (I² = 87%). Subgroup analysis showed a significant effect in moderate-to-severe depression (g = −0.61; 95% CI: −1.17 to −0.05; p = 0.03), but not in minimal-to-mild depression (g = −0.37; 95% CI: −0.79 to 0.04; p = 0.08). Similarly, significant effects were observed in interventions lasting ≥8 weeks (g = −0.36; 95% CI: −0.63 to −0.09; p = 0.008), but not in those <8 weeks. No significant subgroup differences were detected. Risk of bias was generally low, and funnel plot analysis suggested no strong evidence of publication bias.

Conclusions: Probiotic supplementation is associated with a moderate and statistically significant reduction in depressive symptoms and may serve as a promising adjunctive treatment for depression. Further high-quality, large-scale RCTs are needed to determine optimal probiotic formulations, dosing strategies, and long-term effects.