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Efficacy of gut microbiota-targeted interventions for Major Depressive Disorder: A systematic review and network meta-analysis
The connection between gut microbiota imbalance and major depressive disorder (MDD) suggests that targeting the microbiome could serve as a potential intervention. This study investigates which specific microbial modulation strategy is the most effective for reducing depressive symptoms in adults suffering from MDD.
To achieve this, a focused network meta-analysis (NMA) was conducted on monotherapy interventions to minimize pharmacological bias. The researchers searched multiple databases, including PubMed and the Cochrane Library, up to November 2025, without language restrictions.
A thorough screening and risk-of-bias assessment were conducted by two independent reviewers, with discrepancies resolved by consensus or by a third reviewer. The NMA utilized a frequentist random-effects model, and the comparative ranking of the interventions was evaluated using the surface under the cumulative ranking curve (SUCRA).
The analysis included a meta-analysis of 38 randomized controlled trials (RCTs) involving 2,338 participants, and an NMA of 33 RCTs focused solely on monotherapy, including 2,128 subjects. The results highlighted that microbiota-based therapies ranked highest in efficacy within both cohorts (SUCRA: 87.4% for monotherapy; 86.0% for mixed interventions). Notably, microbiota-based therapies yielded significant reductions in depressive symptoms compared to placebo, with a standardized mean difference (SMD) of −0.76 (95% CI, −1.18 to −0.34). Other effective modalities included prebiotics (SMD = −0.55; 95% CI, −0.81 to −0.28), single-strain probiotics (SMD = −0.53; 95% CI, −0.81 to −0.25), multi-strain probiotics (SMD = −0.45; 95% CI, −0.58 to −0.33), and psychobiotics (SMD = −0.36; 95% CI, −0.64 to −0.08). Conversely, synbiotics showed limited efficacy as a standalone option (SMD = −0.19; 95% CI, −0.60 to 0.21).
According to the Grading of Recommendations, Assessment, and Evaluation tool, the confidence in these findings ranged from low to moderate. Although acceptability rates were similar across most interventions, dietary patterns were associated with a higher risk of participant dropout.
In conclusion, gut microbiota-targeted therapies appear to be beneficial for alleviating depressive symptoms in adults with MDD, supported by evidence of moderate reliability. Despite the favorable rankings for microbiota-based treatments, the limited confidence in the evidence demands caution in interpretation, as definitive conclusions about their superiority have yet to be established. Given the comparable acceptability across various interventions, these treatments may serve as useful complementary or alternative strategies. [NPID: Major Depressive Disorder, probiotics, prebiotics, psychobiotics, dietary patterns, randomized controlled trial]
Year: 2026
