Probiotics and Synbiotics Supplementation Reduce Inflammatory Cytokines in Individuals with Prediabetes and Type 2 Diabetes Mellitus: Findings from a Systematic Review Meta-Analysis.

Abstract

Background: Chronic inflammation plays a significant role in the development and progression of diabetes. Despite growing interest in probiotic and synbiotic supplementation, there is limited consensus on their efficacy in modulating inflammatory cytokines. This meta-analysis evaluates the impact of these supplements on inflammatory cytokines in adults with prediabetes and type 2 diabetes mellitus (T2DM).

Methods: A comprehensive search was conducted on online databases from their inception to September 2025 to identify relevant randomized controlled trials (RCTs). Data were extracted from selected studies. The overall effect size was determined using weighted mean differences (WMD) with 95% confidence intervals (CIs) through a random-effects model.

Results: The pooled analysis of 22 RCTs, including 1321 individuals with prediabetes and T2DM, showed that probiotic and synbiotic supplementation significantly reduced C-reactive protein (CRP) (WMD: -0.46 mg/L, 95%CL: [-0.77, -0.15], p=0.003), Interleukin-6 (IL-6) (WMD: -0.43 pg/ml, 95%CI: [-0.76, -0.09], p=0.012) and tumor necrosis factor-Alpha (TNF-α) (WMD: -1.42 pg/ml, 95%CI: [-2.15, -0.69], p<0.001). Subgroup analyses showed that CRP reduction was greatest among participants with baseline CRP ≥3 mg/L, those undergoing longer interventions (≥12 weeks), individuals with T2DM, overweight participants, and when probiotics were administered. IL-6 levels were significantly reduced in obese individuals, particularly with longer treatment durations and synbiotic interventions. TNF-α reductions were most pronounced in long-term interventions (≥12 weeks), especially among T2DM patients with normal BMI, and when probiotics were used.

Conclusion: Probiotic and synbiotic supplementation significantly reduces inflammatory cytokines (CRP, IL-6, TNF-α) in individuals with prediabetes and T2DM, with the strongest effects observed in those with higher baseline inflammation and longer intervention durations. These findings underscore the importance of tailoring supplementation strategies to individual inflammation status, intervention duration, and metabolic profile to optimize therapeutic outcomes.