Dysbiosis and Immune Crosstalk in Experimental Diabetic Periodontitis: A Systemic Review and Meta-Analysis of Preclinical Murine Studies

Diabetes mellitus (DM) fundamentally disrupts the oral microbiome, initiating a dysbiotic shift that drives progressive periodontal tissue breakdown. This transition is mediated by complex, bidirectional immune crosstalk, primarily centering on the upregulation of the Th17/Interleukin-17 (IL-17) inflammatory pathway. This systematic review and meta-analysis quantified the specific impact of this diabetic microbiota on immune activation and periodontal destruction. A comprehensive search of PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library was conducted for studies published up to 2026. Eligible studies included assessing oral/salivary microbiome shifts and their localized or systemic immunological consequences in diabetic periodontitis. A random-effects meta-analysis synthesized standardized mean differences (Hedges’ g) to evaluate the magnitude of these effects. Quantitative synthesis of preclinical data (four studies yielding eight discrete comparisons) revealed that exposure to a diabetic/dysbiotic microbiota significantly increased overall immune activation and periodontal inflammation relative to eubiotic controls (pooled Hedges’ g = 3.73, 95% CI 2.96–4.51). Subgroup analyses confirmed profound, statistically significant effects specifically on the Th17/IL-17 axis (g = 4.03) and periodontal bone destruction pathways (g = 3.37). Preclinical murine data suggests diabetes-associated oral dysbiosis may contribute to periodontal destruction by upregulating the Th17/IL-17 immune axis. However, direct extrapolation to humans is restricted, necessitating further clinical studies to validate these findings.