Causal relationship between oral microbiota and epilepsy risk: Evidence from Mendelian randomization analysis in East Asians

Objective: Gut microbiota can traverse into the brain, activate the vagus nerve, and modulate immune responses and inflammatory processes, thereby influencing the onset of epileptic seizures. However, research on oral microbiota and epilepsy remains limited, and observational studies have been inconsistent. We aim to estimate the potential links between oral microbiota and epilepsy and elucidate which specific oral microbes may directly influence the pathogenesis of epilepsy. Methods: A two-sample MR analysis was conducted using genome-wide association study (GWAS) data specific to OM and epilepsy in East Asian individuals. Single nucleotide polymorphisms (SNPs) independent of confounders served as instrumental variables (IVs) to deduce causality. MR methodologies, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighed mode methods, were utilized. Sensitivity analysis, including Cochrane's Q test, MR-Egger intercept test, and leave-one-out analysis, was applied to confirm the robustness of results. Results: Among the 3117 bacterial taxa examined, we observed that 14 OM, like s_Streptococcus_mitis, s_Streptococcus_pneumoniae, and s_Haemophilus, were positively associated with epilepsy, while 7 OM, like g_Fusobacterium and g_Aggregatibacter, were negatively related to epilepsy. The MR-Egger intercept suggested that no evidence of horizontal pleiotropy was observed (p > 0.05). The leave-one-out analysis validated the robustness of the results. Significance: This study underscores the effect of OM on epilepsy, suggesting potential mechanisms between the OM and epilepsy. Further investigation into the potential role of the OM is needed to enhance our in-depth understanding of the pathogenesis of epilepsy. Plain Language Summary: Previous research has demonstrated that the microbiota may influence the onset of epileptic seizures. We applied 3117 oral microbiota from the newest publicly available database of East Asian populations. Mendelian randomization analysis was utilized to estimate the causal relationship between oral microbiota and epilepsy. Our results showed that a causal effect exists between 21 oral microbiota and epilepsy. We provided genetic evidence for risk assessment and early intervention in epilepsy.