Unveiling the Relationship Between Oral Microbiota and Alzheimer's Disease: A Genetic Instrumental Variable Analysis via Mendelian Randomization

Abstract

Background: The potential relationship between oral microbiota (OM) and Alzheimer's disease (AD) is increasingly recognized, but the exact causal relationship between them remains uncertain. This study aims to reveal the causal relationship between OM and AD. Methods: A two-sample Mendelian randomization (MR) approach was employed to examine the association between 594 OM exposures and AD outcomes. Effect estimates were derived from external genome-wide association study (GWAS) summary statistics, primarily utilizing inverse-variance weighted (IVW) analysis. Sensitivity analyses were conducted to assess the robustness of the findings. In addition, we genetically mapped SNPs corresponding to OM in the MR analysis to identify genes that may link OM to AD. Results: A total of 48 OM exposures exhibited statistically significant associations with AD outcomes (p ≤ 0.05). Of these, 30 were identified at the genus level, 12 at the species level, and six at the family level. Genetic function analyses indicated that OM-related genes are closely linked to the regulation of neurobiological functions, supporting a potential role for OM in the pathogenesis of AD. Conclusion: The findings presented here provide genetic evidence for a causal relationship between OM and AD, offering insights that may guide the future development of prevention and treatment strategies targeting OM in the context of AD.