Abstract
BACKGROUND: Whether alterations in the gut microbiota play a causal role in chronic apical periodontitis (CAP) remains uncertain. A two-sample Mendelian randomization (MR) analysis was used in this study to assess the potential causal effect of gut microbiota on CAP risk. METHODS: Gut microbiota summary statistics were from the MiBioGen consortium's largest GWAS, and CAP data from the FinnGen project. The inverse variance-weighted method was the main analytic approach, and sensitivity analyses verified instrument robustness. RESULTS: Two microbial taxa showed positive causal effect with CAP: Lachnospiraceae FCS020 group (odds ratio [OR] = 1.244, 95% confidence interval [CI]: 1.059-1.461, p = 0.008) and Ruminococcus2 (OR = 1.196, 95% CI: 1.039-1.377, p = 0.013). Conversely, Escherichia-Shigella exhibited an inverse genetic association with CAP risk (OR = 0.746, 95% CI: 0.620-0.897, p = 0.002). Sensitivity analyses supported the stability of these findings and confirmed that the effect estimates were directionally consistent, thereby strengthening confidence in the primary results. CONCLUSIONS: This MR analysis provides evidence of a genetic relationship between gut microbiota composition and susceptibility to CAP. The findings broaden our understanding of microbial changes in CAP-affected tissues, and suggest a genetic association between alterations in the composition of the gut microbiota and CAP risk.