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

Xie et al., 2025 | Front Cell Infect Microbiol | Meta Analysis

Citation

Xie Yanpeng, Zheng Yingkang, ... Cai Xiaojun. Meta-analytical insight on probiotic metabolites and inflammatory markers in diabetes. Front Cell Infect Microbiol. 2025;15:1677671. doi:10.3389/fcimb.2025.1677671

Abstract

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: These findings support the adjunctive use of targeted, SCFA-oriented probiotic formulations (e.g., Lactobacillus plantarum, Lactobacillus casei, Bifidobacterium longum 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.

Key Findings

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 o

Outcomes Measured

  • C-reactive protein
  • inflammatory markers

Population

Field Value
Population type 1 and type
Sample Size See abstract
Age Range See abstract
Condition diabetes

MeSH Terms

  • Probiotics
  • Humans
  • Synbiotics
  • Biomarkers
  • Fatty Acids, Volatile
  • Gastrointestinal Microbiome
  • Inflammation
  • Randomized Controlled Trials as Topic
  • Diabetes Mellitus, Type 2
  • Interleukin-10
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Diabetes Mellitus, Type 1

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Systematic Review
  • Vertical: probiotics

Provenance


Source extracted via PubMed E-utilities API on 2026-04-09