Clinical value of probiotics as adjunctive therapy for diabetic nephropathy: a meta-analysis and trial sequential analysis.

Objective: To comprehensively assess the clinical effectiveness of probiotic supplementation in individuals with diabetic nephropathy (DN). Methods: Randomized controlled trials (RCTs) evaluating probiotics for DN were retrieved from eight databases from inception to January 2026. Data on study characteristics, outcome measures, and risk of bias were independently extracted. Meta-analyses were conducted using Review Manager version 5.3, while trial sequential analysis (TSA) was performed with TSA version 0.9.5.10 beta. Potential publication bias was examined using Egger's regression test. Results: Nine RCTs encompassing 644 participants met the inclusion criteria. Pooled analyses indicated that probiotic supplementation was associated with significant reductions in serum creatinine (mean difference [MD] -0.10 mg/dL, 95% confidence interval [CI] -0.14 to -0.06), blood urea nitrogen (BUN) (MD - 2.76 mg/dL, 95% CI - 5.40 to -0.11), fasting plasma glucose (MD - 0.63 mmol/L, 95% CI - 0.80 to -0.46), 2-h postprandial blood glucose (2 h PBG) (MD - 0.66% mmol/L, 95% CI -1.10 to -0.22), glycated hemoglobin (HbA1c) (MD -0.40%, 95% CI -0.72 to -0.09), triglycerides (MD -19.17 mg/dL, 95% CI -35.14 to -3.20), total cholesterol (MD -11.68 mg/dL, 95% CI -20.37 to -2.99), low-density lipoprotein cholesterol (MD -12.72 mg/dL, 95% CI -18.76 to -6.67), high-sensitivity C-reactive protein (MD -1.69 mg/L, 95% CI -2.38 to -1.00), and malondialdehyde (MD - 0.52 μmol/L, 95% CI -0.91 to -0.13). However, no statistically significant improvements were detected in estimated glomerular filtration rate, 24-h urinary protein excretion, insulin levels, high-density lipoprotein cholesterol, or total antioxidant capacity. TSA supported the reliability of all significant findings except for BUN and triglycerides. Egger's test revealed no evidence of publication bias for most outcomes. Conclusion: Probiotics reduce circulating inflammation and oxidative stress levels in patients with DN, highlighting their potential as an adjunctive therapy, although their effects on glycolipid metabolism and kidney function appear to be modest. Nevertheless, given the limitations of small sample sizes and regional concentration, these findings warrant further validation through multicenter RCTs involving diverse ethnic populations. Systematic review registration: The systematic review was prospectively registered in PROSPERO (CRD420261375372). The registration is publicly accessible at https://www.crd.york.ac.uk/prospero/.