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.

PROSPERO: CRD420251128261