# Efficacy of probiotic intervention in unmedicated depression: a systematic review and meta-analysis

## TL;DR

This study finds that probiotics may slightly reduce depressive symptoms in unmedicated adults, but the effect is small and needs further confirmation.

## Contribution

The paper provides a systematic review and meta-analysis of probiotics as monotherapy for depression in unmedicated individuals.

## Key findings

- Probiotic monotherapy showed a small but significant reduction in depressive symptoms.
- Greater benefit was observed in mild to moderate depression compared to major depressive disorder.
- Safety outcomes showed no significant difference between probiotic and placebo groups.

## Abstract

To assess the independent efficacy and safety of probiotics in unmedicated adults with depression, with a focus on studies approximating monotherapy conditions.

This systematic review and meta-analysis followed PRISMA 2020 guidelines and was registered with PROSPERO (CRD420251015474). Four major databases were searched through March 2025 for randomized controlled trials (RCTs) investigating probiotic monotherapy in individuals with depression not receiving psychotropic treatment. All forms of standardized probiotic formulations (e.g., capsules, sachets) were eligible. The primary outcome was the change in validated depression rating scales. Standardized mean differences (SMDs) were synthesized using a random-effects model. Sensitivity and subgroup analyses addressed intervention type, assessment method (self-report vs. clinician-rated scales), and funding source. Safety outcomes were systematically assessed.

Six RCTs with 341 randomly assigned participants (169 probiotic, 172 placebo) were included. Probiotic monotherapy was associated with a small but statistically significant reduction in depressive symptoms (SMD = −0.38, 95% CI: −0.57 to −0.18, p = 0.0002, I² = 51%). Exploratory subgroup analysis indicated potential greater benefit in mild to moderate depression compared to major depressive disorder. Sensitivity analysis excluding industry-funded trials or studies with adjunctive agents resulted in non-significant findings (SMD = −0.21, 95% CI: −0.65 to 0.23, p = 0.35). Minor adverse events were reported, with no significant difference between groups and no serious adverse events.

Probiotic monotherapy may provide modest improvement in depressive symptoms and is generally safe for unmedicated individuals with mild to moderate depression. Given the small effect size, possible industry-related bias, and study heterogeneity, these findings should be interpreted cautiously. Larger, independently-funded RCTs are warranted to confirm efficacy and clarify mechanisms.

https://www.crd.york.ac.uk/prospero/, iidentifier CRD420251015474.