Effects of probiotic supplementation on inflammatory biomarkers in patients with depression: A systematic review and meta-analysis of randomized controlled trials.

Background

Chronic low-grade inflammation has been widely acknowledged as an important pathophysiological mechanism underlying depression. Probiotics may alleviate depressive symptoms by modifying the microbiota-gut-brain axis and regulating inflammatory responses. The purpose of this systematic review and meta-analysis was to assess the effect of probiotic supplementation on circulating inflammatory biomarkers in depressed individuals.

Methods

A systematic search of the literature was conducted in PubMed and Google Scholar from the beginning until October 2025. Scopus, Embase, Web of Science, and the Cochrane Library were also screened. Randomized controlled trials assessing the impact of probiotic supplementation on serum inflammatory biomarkers in adult patients with depression were included. Random-effects models were used to compute pooled weighted mean differences (WMDs) and 95% confidence intervals (CIs).

Results

Ten randomized controlled trials with 486 participants were included in our study. Significant reductions in serum concentrations of C-reactive protein (CRP) (WMD = -0.74; 95% CI: -1.18 to -0.30) and tumor necrosis factor-alpha (TNF-α) (WMD = -0.23; 95% CI: -0.43 to -0.04), and a borderline reduction in interleukin-1 beta (IL-1β) (WMD = -0.03; 95% CI: -0.07 to 0.00) were observed. However, there were no significant effects for interleukin-6 (IL-6) (WMD = -0.10; 95% CI: -0.22 to 0.03) or interleukin-10 (IL-10) (WMD = 0.08; 95% CI: -0.22 to 0.38).

Conclusions

Probiotic supplementation was associated with a significant decrease in CRP and TNF-α, and a borderline reduction in IL-1β in patients with depression. No such significant results were reached for IL-10 or IL-6. To validate these effects and identify the best probiotic formulations and treatment protocols, larger and longer-term randomized trials are required.