Microbiome-based Interventions in Mental Health: A Decade of Systematic Evidence on Depression, Anxiety, and Stress

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 ۲۶ human studies (۲۰۱۵-۲۰۲۵): ۱۹ randomized controlled trials (RCTs), ۳ cohort studies, ۳ cross-sectional studies, and ۱ case-control study. Data were extracted on study design, interventions, microbial measures, outcomes, and risk of bias (RoB). Results: Probiotics/prebiotics (۱۰⁹-۱۰¹⁰ CFU/day for ۶-۱۲ weeks) improved outcomes in ۱۳/۱۹ RCTs (۶۸.۴%). Multi-strain and combined interventions (e.g. with an SSRI or diet) produced the most consistent effects; ۶/۱۹ RCTs (۳۱.۶%) 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 ۱۳/۱۹ RCTs and moderate in ۶/۱۹ 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.

کلیدواژه ها:

Gastrointestinal microbiome ، Probiotics ، Prebiotics ، Depressive disorder ، Anxiety disorders ، Stress ، Psychological