Effects of Prebiotics and Probiotics on Symptoms of Depression and Anxiety in Clinically Diagnosed Samples: Systematic Review and Meta-analysis of Randomized Controlled Trials

Nutr Rev. 2024 Dec 28:nuae177. doi: 10.1093/nutrit/nuae177. Online ahead of print.

Abstract

Context: The use of prebiotics and probiotics as a treatment for psychiatric conditions has gained interest due to their potential to modulate the gut-brain axis. This review aims to assess the effectiveness of these interventions in reducing symptoms of depression and anxiety in psychiatric populations.

Objective: The aim was to comprehensively review and appraise the effectiveness of prebiotic, probiotic, and synbiotic interventions in reducing clinical depression and anxiety symptoms.

Data sources: Systematic searches were conducted across Embase, Medline, PsycINFO, CINAHL, Cochrane Library, and Science Citation Index from database inception to May 22, 2023.

Data extraction: Randomized controlled trials investigating prebiotic, probiotic, or synbiotic interventions for treating clinical depression or anxiety symptoms in clinical samples were included. Data were extracted on study characteristics, intervention details, and outcome measures. The Cochrane Collaboration Tool was used to assess the risk of bias.

Data analysis: The standardized mean difference (SMD) was calculated using Hedge's g as the metric of effect size. A random-effects model was applied to estimate pooled effect sizes with 95% CIs. Subgroup analyses were performed based on study characteristics, methodological factors, and intervention types. Sensitivity analyses excluded studies with a high risk of bias.

Results: Twenty-three RCTs involving 1401 patients met the inclusion criteria, with 20 trials providing sufficient data for meta-analysis. Of these, 18 trials investigated probiotics for depression, 9 trials assessed probiotics for anxiety, and 3 trials examined prebiotics for depression. Probiotics demonstrated a significant reduction in depression symptoms (SMD: -0.96; 95% CI: -1.31, -0.61) and a moderate reduction in anxiety symptoms (SMD: -0.59; 95% CI: -0.98, -0.19). Prebiotics did not show a significant effect on depression (SMD: -0.28; 95% CI: -0.61, 0.04). High heterogeneity was observed across studies, and subgroup analyses indicated that study duration and probiotic formulations contributed to the variation in effect sizes.

Conclusion: Probiotics showed substantial reductions in depression symptoms and moderate reductions in anxiety symptoms. Prebiotics showed a nonsignificant trend toward reducing depression. An adjunctive mental health treatment approach that diagnoses, monitors, and treats the gut microbiome alongside traditional pharmacological treatment holds promise for clinical practice.

Systematic review registration: PROSPERO registration no. CRD42023424136.

Keywords: anxiety; depression; meta-analysis; prebiotics; probiotics.

Plain language summary

What is already known on this topic? Rates of depression and anxiety continue to rise, and new treatment options are needed. There is clear evidence that the gut–brain axis is implicated in depression severity. Several systematic reviews and meta-analyses have shown a small–moderate effect of probiotics in alleviating symptoms of depression in clinical and nonclinical populations. What this study adds. There still remains a large gap in understanding the effectiveness and clinical relevance of gut microbiota interventions for clinically diagnosed populations experiencing symptoms of depression and anxiety. This is the largest comprehensive meta-analytic review to examine the effectiveness of pre- and probiotic use in alleviating symptoms of depression and anxiety severity for clinically diagnosed populations experiencing comorbid depression and anxiety. How this study might affect research, practice or policy. Findings from this study indicate that up to 8 weeks of probiotic use compared with placebo is effective in reducing depressive and anxiety symptoms in clinically diagnosed patients. Single-strain and multi-strain probiotics showed moderate to large effects on reducing depression and anxiety severity, with single-strain probiotics showing the strongest benefit. Prebiotics appear to have beneficial effects on anxiety symptoms, but future research is needed to substantiate these findings. Larger trials exploring depression remission rates and treatment dosage trajectories are recommended.