Journal Article

Meta-analytical insight on probiotic metabolites and inflammatory markers in diabetes

Zheng, Yingkang, Jiang, Fan, Xie, Yanpeng, Cai, Xiaojun

2025

Overview

Systemic inflammation is a hallmark of diabetes mellitus and contributes to insulin resistance and disease progression. Emerging evidence suggests that gut microbiota and their metabolites, particularly short-chain fatty acids (SCFAs), play a crucial role in modulating immune responses. Probiotics and synbiotics are increasingly explored for their potential to mitigate inflammation via microbiota-targeted mechanisms. This study aims to evaluate the effects of probiotic and synbiotic supplementation on inflammatory markers and microbial metabolites in individuals with type 1 and type 2 diabetes through meta-analytical techniques. A total of 46 randomized controlled trials (RCTs) comprising 3,580 diabetic patients were included following PRISMA guidelines. Meta-analyses were performed using random-effects models to assess changes in inflammatory markers (CRP, IL-6, TNF-α, IL-10) and SCFA levels (butyrate, propionate, acetate). Subgroup analyses and meta-regressions were conducted to identify effect modifiers such as intervention duration, formulation type (probiotic vs. synbiotic), and SCFA concentrations. Probiotic/synbiotic interventions led to significant reductions in CRP (SMD = -0.54), IL-6 (SMD = -0.41), and TNF-α (SMD = -0.48), along with an increase in IL-10 (SMD = +0.38). SCFA levels rose significantly, with butyrate showing the strongest effect (SMD = +0.46). Meta-regression revealed that butyrate levels, synbiotic use, and intervention duration ≥8 weeks were strong predictors of anti-inflammatory efficacy. Multi-strain and synbiotic interventions were more effective than single-strain or probiotic-only formulations. Sensitivity analyses confirmed the robustness of findings, and publication bias was minimal. These findings support the adjunctive use of targeted, SCFA-oriented probiotic formulations (e.g., with inulin/FOS, ≥10^9-10^10 CFU/day) to mitigate metabolic inflammation alongside standard care. Strain- and dose-standardized RCTs should confirm impacts on glycemic and cardiometabolic outcomes.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Acetic acid / Biomarkers / Biomarkers - blood / C-Reactive Protein - analysis / Cellular and Infection Microbiology / Clinical trials / Cytokines / Diabetes / diabetes mellitus / Diabetes mellitus (insulin dependent) / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 1 / Diabetes Mellitus, Type 2 / Dietary supplements / Disease resistance / Fatty Acids, Volatile - metabolism / Gastrointestinal Microbiome / gut microbiota / Humans / Immune response / Inclusion / Inflammation / inflammatory markers / Insulin resistance / Interleukin 10 / Interleukin 6 / Interleukin-10 - blood / Interleukin-6 - blood / Intervention / Intestinal microflora / Meta-analysis / Metabolism / Metabolites / Microbiota / Probiotics / Probiotics - administration & dosage / Probiotics - metabolism / Randomized Controlled Trials as Topic / Sensitivity analysis / short-chain fatty acids (SCFAs) / Synbiotics - administration & dosage / systemic inflammation / Tumor Necrosis Factor-alpha - blood / Tumor necrosis factor-TNF / Tumor necrosis factor-α