The Effect of Probiotics on Obesity with Comorbid Depression: A Systematic Review and Meta-Analysis

Aims/Background Obesity and depression frequently co-occur, and the relationship between them is bidirectional. Being obese or overweight increases the risk of depression, and conversely, depression increases the risk of obesity or overweight. Emerging clinical research has shown that probiotics may be effective in treating obesity and associated depression. Modulating gut microbiota with probiotics may improve obesity-related depression, but current evidence is inconsistent. Methods We systematically searched PubMed, EMBASE, Web of Science, and Cochrane Library for randomized controlled trials examining probiotics for depression in obese adults. Mean difference (MD) in depression scores between probiotic and placebo groups was pooled across studies using random-effects models. Heterogeneity was assessed using I² to explain heterogeneity in meta-regression analysis. To detect the publication bias of the included studies, a funnel plot, and Begg and Egger tests, were used. Possible heterogeneity moderators were detected by subgroup and sensitivity analyses, Galbraith plot, and graphic display of study heterogeneity (GOSH) analysis. Leave-one-out and Influence analyses were performed to assess sensitivity. Results Five trials (n = 488) were included. Overall, probiotics did not significantly improve depressive symptoms versus placebo (MD = 0.08, 95% confidence interval [CI] = -0.63 to 0.79, p = 0.82). Considerable heterogeneity among studies was observed (I² = 63%). In subgroup analyses, probiotics significantly reduced depression as measured by the Edinburgh Postnatal Depression Scale (MD = -0.60, 95% CI = -1.17 to -0.03, p = 0.04) with no heterogeneity (I² = 0%). Probiotics also decreased depressive symptoms after 12 weeks of supplementation (MD = -0.78, 95% CI = -1.58 to -0.01, p = 0.05) versus placebo. No publication bias was found using Begg and Egger tests. The GOSH diagnostics revealed three outliers, among the clusters identified by K-means, DBSCAN (Density-based spatial clustering of applications with noise algorithm), and GMM (Gaussian Mixture Model) analyses. Conclusion Overall, probiotics did not improve depressive symptoms in obesity. However, beneficial effects were observed with the Edinburgh Postnatal Depression Scale and short-term use of probiotic. Additional rigorous randomized controlled trials are warranted to elucidate the therapeutic potential of probiotics for obesity-related depression.