Genetic Connectivity of Gut Microbiota and Oral Ulcers: A Mendelian Randomization Study

Objectives: The aim of this study was to reveal the relationship, if any, between gut microbiota and oral ulcers. Methods: We performed a 2-sample Mendelian randomization (MR) study to estimate the roles of gut microbiota in mouth ulcers. The summary datasets of gut microbiota were from the largest genome-wide association study (GWAS) conducted by MiBioGen, and data of mouth ulcers were obtained from UK Biobank. Random effect inverse variance-weighted, weighted median, MR Egger, simple mode and weighted mode were used to estimate the relationship. Sensitivity analyses were conducted to assess the heterogeneity and pleiotropy of instrumental variables. MR Steiger filtering was also applied to orient the causal direction. Results: Three gut microbiota taxa were positively associated with mouth ulcers: Holdemania (odds ratio [OR] = 1.005, 95% confidence interval [CI]: 1.001-1.009, P = .019), Oxalobacter (OR = 1.004, 95% CI: 1.000-1.007, P = .032), and Ruminococcaceae UCG011 (OR = 1.006, 95% CI: 1.001-1.011, P = .029), while 4 gut microbiota taxa were negatively associated with mouth ulcers: Actinobacteria (OR = 0.992, 95% CI: 0.985-1.000, P = .042), Lactobacillales (OR = 0.995, 95% CI: 0.990-1.000, P = .034), Oscillospira (OR = 0.990, 95% CI: 0.984-0.997, P = .007) and Phascolarctobacterium (OR = 0.992, 95% CI: 0.986-0.997, P = .003). Sensitivity analyses validated the robustness of the association in between. Conclusions: This MR study identified a strong association between the quality of gut microbiota and oral ulcers. The findings are likely to expand the therapeutic targets for mouth ulcers.