Causal effects of gut microbiota on periodontitis risk: a meta-analysis of Mendelian randomization studies

OBJECTIVE: To evaluate the causal relationship between gut microbiota and periodontitis (PD) by synthesizing Mendelian randomization (MR) studies across taxonomic levels. METHODS: We systematically searched five databases to November 2024 for MR studies linking gut microbiota (Order/Family/Genus/Species) to PD. Study-level odds ratios (ORs) were pooled with random-effects models; small-study effects were explored; and multiplicity was controlled with Benjamini-Hochberg false discovery rate (FDR)-within each taxonomic level (primary) and globally across all taxa (sensitivity). Reporting and certainty were appraised using STROBE-MR and a GRADE framework adapted for MR. Meta-analyses used Stata 15.1. RESULTS: Six MR studies were included. Enterobacterales (OR = 1.30, 95% CI: 1.17-1.44) and Pasteurellales (OR = 1.12, 95% CI: 1.04-1.21) remained significant after within-level FDR. At the genus/species levels, Granulicatella and Prevotella salivae were risk-increasing, whereas Butyricicoccus and Ruminiclostridium 6 were protective (significant within-level FDR; suggestive under global FDR). Across taxa combined, the pooled association indicated increased PD risk (OR = 1.18, 95% CI: 1.11-1.26). CONCLUSIONS: This meta-analysis supports a causal contribution of specific gut taxa to PD risk. Risk-increasing Orders (Enterobacterales, Pasteurellales) and risk-modifying genera/species (Granulicatella, Prevotella salivae; Butyricicoccus, Ruminiclostridium 6) may inform hypothesis-driven prevention and mechanistic studies.