The efficacy and acceptability of Lactobacillus reuteri for the treatment of depression: A systematic review and meta-analysis

Gen Hosp Psychiatry. 2025 Jul-Aug:95:122-132. doi: 10.1016/j.genhosppsych.2025.05.004. Epub 2025 May 4.

Abstract

Introduction: Some preclinical and clinical studies have demonstrated the positive effect of Lactobacillus reuteri (L. reuteri) supplementation on depressive symptoms. We conducted an updated systematic review on this topic.

Method: PubMed, EMBASE, Cochrane, Web of Science, and international trial registries were searched. We included randomized controlled trials (RCTs) and animal experiments on the use of mixed probiotics containing L. reuteri in the treatment of depression. Analyses were done using Review Manager version 5.4 and Stata 18.0.

Results: In total, 12 RCTs including 1258 patients were included. The efficacy of the mixed probiotics containing L. reuteri in the treatment of depression was superior to the control group (SMD: -0.44, 95 %CI: -0.72 to -0.16). In terms of acceptability, there was no significant difference between the probiotic and control groups (OR: 1.04, 95 %CI: 0.75 to 1.45). In 9 animal experiments, mixed probiotics containing L. reuteri improved the symptoms of anxiety and depression. Subgroup analyses showed patients using multi-strain interventions (SMD: -0.56, 95 %CI: -0.97 to -0.15), having depressive symptoms (SMD: -0.39, 95 %CI: -0.74 to -0.03), and other clinical populations (SMD: -0.59, 95 %CI: -1.06 to -0.13), age < 60 years (SMD: -0.52, 95 %CI: -0.88 to -0.15), female patients (SMD: -0.45, 95 %CI: -0.78 to -0.13) may benefit more.

Conclusion: Mixed probiotics containing L. reuteri ameliorated depressive symptoms in patients and depression-like behaviors in animals. Combined microbiota seems to be more effective than single strain intervention in the treatment of depression. Patients with depressive symptoms, other clinical populations, age < 60 years, female patients may benefit more from probiotics. L. reuteri alone did not improve depressive symptoms.

Keywords: Depression; Lactobacillus reuteri; Microorganism; Probiotic.

Publication types

  • Systematic Review
  • Meta-Analysis

MeSH terms

  • Animals
  • Depression* / therapy
  • Depressive Disorder* / therapy
  • Humans
  • Limosilactobacillus reuteri*
  • Outcome Assessment, Health Care*
  • Probiotics* / administration & dosage
  • Probiotics* / pharmacology
  • Probiotics* / therapeutic use
  • Randomized Controlled Trials as Topic