Li Zhichao, Kang Yihan, Li Shuai, Guo Shiqi, Zheng Hui
Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, China.
Brain Behav. 2025 Aug;15(8):e70753. doi: 10.1002/brb3.70753.
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.
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.
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.
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.
口腔微生物群（OM）与阿尔茨海默病（AD）之间的潜在关系日益受到认可，但它们之间的确切因果关系仍不确定。本研究旨在揭示OM与AD之间的因果关系。
采用两样本孟德尔随机化（MR）方法来检验594种OM暴露与AD结局之间的关联。效应估计值来自外部全基因组关联研究（GWAS）汇总统计数据，主要采用逆方差加权（IVW）分析。进行敏感性分析以评估研究结果的稳健性。此外，我们在MR分析中对与OM对应的单核苷酸多态性（SNP）进行基因定位，以确定可能将OM与AD联系起来的基因。
共有48种OM暴露与AD结局表现出统计学上的显著关联（p≤0.05）。其中，30种在属水平上被鉴定出来，12种在种水平上，6种在科水平上。基因功能分析表明，与OM相关的基因与神经生物学功能的调节密切相关，支持了OM在AD发病机制中的潜在作用。
本研究结果为OM与AD之间的因果关系提供了遗传学证据，为指导未来在AD背景下针对OM的预防和治疗策略的开发提供了见解。
