Do probiotics reduce systemic inflammation in depression? A systematic review and meta-analysis

Several studies have revealed the role of inflammation in the pathogenesis of depression. Previous studies have reported elevated level of inflammatory markers such as C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in patients with depression. While probiotics appear to exert beneficial effects to alleviate the inflammation state. This systematic review and meta-analysis aimed to investigate the effect of probiotics on inflammatory markers among depressive patients. A comprehensive systematic search was performed in PubMed, Scopus, Web of Science, and google scholar databases up to April 2026. We included randomized controlled trials (RCTs) that examined the efficacy of probiotics across inflammatory markers in subjects with depression. It has been registered in PROSPERO (CRD420261460681). In total, eleven RCTs were included in this study. The pooled estimates of studies illustrated that probiotic supplementation is associated with significant reduction in CRP level in patients with depression (SMD: -0.55, 95% CI: -1.07, -0.04; P = 0.036, I 2 = 72.3%; P-heterogeneity = 0.003). Moreover, subgroup analysis indicated that probiotics exert more beneficial effects in CRP level in longer duration (≥ 8 weeks). While, substantial heterogeneity among the included studies precluded any meaningful pooled analysis of IL-6 (SMD: -0.04, 95% CI: -0.57, 0.48; P = 0.868, I 2 = 81.2%; P-heterogeneity < 0.001), IL-1β (SMD: 0.00, 95% CI: -0.20, 0.21; P = 0.970, I 2 = 0.00%; P-heterogeneity = 0.659), and TNF-α (SMD: -0.40, 95% CI: -0.83, 0.04; P = 0.074, I 2 = 77.3%; P-heterogeneity < 0.001). The current study demonstrated that probiotics could have ameliorative effects on CRP level in patients with depression. However, further studies are needed to investigate the real effect of probiotics on IL-6, IL-1β, and TNF-α level.