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Chukwu O O, Igbokwe M C, Efiok A, Alagbonsi A I. Microbiome-based Interventions in Mental Health: A Decade of Systematic Evidence on Depression, Anxiety, and Stress. Iran J Health Sci 2026; 14 (3) :211-226
URL: http://jhs.mazums.ac.ir/article-1-1104-en.html

Background and Purpose: The gut–brain axis links microbiota to mental health, but evidence on probiotic/prebiotic interventions for depression, anxiety, and stress remains heterogeneous.
Materials and Methods: This study aimed to synthesize human evidence on gut microbiota-mental health associations and evaluate microbiome-targeted interventions. We reviewed 26 human studies (2015-2025): 19 randomized controlled trials (RCTs), 3 cohort studies, 3 cross-sectional studies, and 1 case-control study. Data were extracted on study design, interventions, microbial measures, outcomes, and risk of bias (RoB).
Results: Probiotics/prebiotics (10⁹-10¹⁰ CFU/day for 6-12 weeks) improved outcomes in 13/19 RCTs (68.4%). Multi-strain and combined interventions (e.g. with an SSRI or diet) produced the most consistent effects; 6/19 RCTs (31.6%) reported null effects, suggesting strain- and context-dependent effects. Observational studies linked reduced microbial diversity and dysbiosis to poorer mental health. The RoB was low in 13/19 RCTs and moderate in 6/19 RCTs; observational studies had a moderate RoB, primarily because of confounding. Publication bias was suspected based on funnel plot asymmetry.
Conclusion: Multi-strain probiotics may reduce symptoms of depression, anxiety, and stress, whereas microbial diversity may be protective. Limitations include outcome heterogeneity, possible publication bias, and limited long-term data. Future multi-center RCTs with harmonized measures are needed.