Causal associations between gut microbiota and five common oral lesions: A two-sample Mendelian randomization study

Previous studies have investigated the relationship between gut microbiota (GM) and oral lesions, but the reported associations across microbial taxa and oral conditions have been inconsistent. This 2-sample Mendelian randomization study using summary-level GWAS data aimed to clarify the causal links between GM and 5 oral conditions: loose teeth, toothache, bleeding gums, painful gums, and mouth ulcers. GM data were obtained from the MiBioGen consortium, while outcome data were derived from the Neale Lab and MRC-IEU consortium. We applied inverse variance weighted (IVW) and complementary MR methods to estimate causal effects, with reverse MR performed to test the possibility of reverse causality, and multivariable MR (MVMR) used to assess whether associations persisted after adjusting for conventional risk factors. The IVW method identified 42 potential associations between GM and oral conditions. For example, the Mollicutes class and Tenericutes phylum were negatively associated with loose teeth (Mollicutes: odds ratio [OR] = 0.9936, 95% confidence interval [CI]: 0.9894 to 0.9978, P = .0029), whereas the Slackia genus showed a positive association with toothache (OR = 1.0096, 95% CI: 1.0050 to 1.0142, P = 3.98 × 10-5). These associations were further confirmed in replication analyses, and MVMR demonstrated that they remained significant after accounting for established risk factors. The findings suggest robust causal links between specific GM taxa and oral conditions, offering novel insights into the GM-oral health axis and highlighting potential preventive or therapeutic targets for oral care.