探索肠道微生物群与阿尔茨海默病之间的因果关系：一项双向孟德尔随机化研究。

Exploring Causal Relationships Between Gut Microbiota and Alzheimer's Disease: A Bidirectional Mendelian Randomization Study.

作者信息

Chen Anqi, Wang Yuquan, Hu Yue-Qing

机构信息

State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.

Shanghai Center for Mathematical Sciences, Fudan University, Shanghai, China.

出版信息

J Alzheimers Dis Rep. 2024 Jul 5;8(1):1031-1040. doi: 10.3233/ADR-240071. eCollection 2024.

DOI:10.3233/ADR-240071

PMID:39114549

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11305842/

Abstract

BACKGROUND

Many observational studies have investigated the link between the gut microbiota and Alzheimer's disease (AD), but the causality remains uncertain.

OBJECTIVE

This study aimed to evaluate the causal impact of gut microbiota on AD.

METHODS

A two-sample Mendelian randomization (MR) study was conducted employing summary data. Summary statistics for AD were from the latest genome-wide association study (cases and proxy cases: 85,934; controls: 401,577). Summary data for gut microbiota were acquired from MiBioGen consortium. Causal effect estimations primarily relied on the inverse variance weighting method along with the sensitivity analyses for testing for pleiotropy and heterogeneity. Additionally, reverse MR analyses were performed to examine potential reverse causality.

RESULTS

Seven gut microbiota were identified as associated with AD risk. Order (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.03-1.24, = 0.01), Family (OR 1.07, 95% CI 1.01-1.13, = 0.01), and Genus (OR 1.07, 95% CI 1.00-1.13, = 0.04) were correlated with an elevated likelihood of AD, while Class (OR 0.87, 95% CI 0.79-0.95, = 0.00), Genus (OR 0.87, 95% CI 0.78-0.97, = 0.01), Genus (OR 0.94, 95% CI 0.89-0.99, = 0.03), and Genus (OR 0.94, 95% CI 0.89-1.00, = 0.04) exerted beneficial impact in mitigating AD. No statistically significant reverse causality was found between AD and each of these seven specific gut microbiota species.

CONCLUSIONS

This study unveiled a causal link between certain gut microbiota and AD, offering new insights for advancing clinical treatments.

摘要

背景

许多观察性研究已调查了肠道微生物群与阿尔茨海默病（AD）之间的联系，但因果关系仍不确定。

目的

本研究旨在评估肠道微生物群对AD的因果影响。

方法

采用汇总数据进行了一项两样本孟德尔随机化（MR）研究。AD的汇总统计数据来自最新的全基因组关联研究（病例和替代病例：85,934例；对照：401,577例）。肠道微生物群的汇总数据从MiBioGen联盟获取。因果效应估计主要依赖于逆方差加权法以及用于检验多效性和异质性的敏感性分析。此外，进行了反向MR分析以检查潜在的反向因果关系。

结果

七种肠道微生物群被确定与AD风险相关。目（优势比[OR]1.13，95%置信区间[CI]1.03 - 1.24，P = 0.01）、科（OR 1.07，95% CI 1.01 - 1.13，P = 0.01）和属（OR 1.07，95% CI 1.00 - 1.13，P = 0.04）与AD发生可能性增加相关，而纲（OR 0.87，95% CI 0.79 - 0.95，P = 0.00）、属（OR 0.87，95% CI 0.78 - 0.97，P = 0.01）、属（OR 0.94，95% CI 0.89 - 0.99，P = 0.03）和属（OR 0.94，95% CI 0.89 - 1.00，P = 0.04）在减轻AD方面发挥有益作用。在AD与这七种特定肠道微生物群中的每一种之间未发现具有统计学意义的反向因果关系。