Clinical effects of probiotic supplementation on depressive symptom severity in adults with depressive disorders: a systematic review and meta-analysis

Abstract

Probiotic supplementation has been investigated as a potential adjunctive treatment for depressive disorders, but its clinical efficacy and safety remain uncertain. This systematic review and meta-analysis aimed to evaluate the effects of probiotics on depressive symptom severity, clinical response, remission, treatment discontinuation, and adverse events in adults with clinically diagnosed depressive disorders. This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to May 8, 2026. Randomized controlled trials (RCTs) evaluating orally administered probiotics against placebo or another non-probiotic control were included. Continuous outcomes were summarized as standardized mean differences (SMDs) using Hedges’ g, and dichotomous outcomes as risk ratios (RRs), with 95% confidence intervals (CIs). Random-effects models used restricted maximum likelihood estimation with Hartung–Knapp adjustment. Heterogeneity was assessed using Cochran’s Q, I 2 , and τ 2 , and robustness was examined using leave-one-out sensitivity analysis. Nine RCTs involving 460 participants were included. Probiotic supplementation was associated with a modest reduction in depressive symptom severity (SMD, −0.43; 95% CI, −0.73 to −0.12; I 2 = 46.8%; τ 2 = 0.069). The 95% prediction interval ranged from −1.10 to 0.25. Leave-one-out estimates ranged from −0.52 to −0.38, with all 95% CIs excluding zero. No significant effect modification was detected across formulation, dose, duration, treatment context, diagnostic population, or outcome-rater subgroups. Clinical response and remission were available from one trial and remained inconclusive (RR, 0.75; 95% CI, 0.32–1.77; and RR, 0.42; 95% CI, 0.08–2.19, respectively). All-cause discontinuation did not differ clearly between groups (seven RCTs; RR, 1.15; 95% CI, 0.67–1.98). Adverse-event evidence was limited and inconsistently reported. Probiotic supplementation may modestly reduce depressive symptom severity, particularly as an adjunct to established treatment. However, the prediction interval included the null, and evidence regarding clinical response, remission, and safety remained inconclusive. Larger, adequately powered RCTs with standardized clinically meaningful outcomes and strain-specific reporting are required.