Ren Zhao-Lin, Zhou Hai-Hong, Chen Chu-Pei, He Hao, Wang Duo-Lao, Liu Zhou
Department of Neurology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, Guangdong Province, China.
Department of Clinical Medicine, Guangdong Medical University, Zhanjiang 524000, Guangdong Province, China.
World J Clin Cases. 2024 Jun 6;12(16):2780-2788. doi: 10.12998/wjcc.v12.i16.2780.
Existing evidence suggests that gut microbiota represent a significant environmental risk factor for various forms of dementia, including Alzheimer's dementia, vascular dementia, and dementia in other diseases classified elsewhere. However, the exact causal relationships between gut microbiota and the different forms of dementia or their subtypes remain unclear.
To investigate putative causal relationships between gut microbiota and dementia or its subtypes using Mendelian randomization (MR) analysis.
A bidirectional, two-sample, MR analysis was conducted utilizing publicly available gut microbiota-related genome-wide association study (GWAS) summary data from the MiBioGen consortium alongside GWAS summary statistics for dementia and its subtypes from the FinnGen consortium. Instrumental variables were selected according to the fundamental tenets of MR and their strengths were evaluated using the -statistic. Five MR methods were employed, and the robustness of our findings was validated. To account for multiple comparisons, we applied the Bonferroni method for -value adjustment.
We identified several gut microbiota taxa exhibiting putative causal relationships with dementia or its subtypes, potentially serving as risk or protective factors for the disease. In addition, reverse MR analysis indicated that the relative abundance of several gut microbiota taxa might be influenced by dementia or its subtypes. An exhaustive sensitivity analysis confirmed the absence of heterogeneity and horizontal pleiotropy. After applying correction for multiple testing, we observed that the order Bacillales (odds ratio: 0.830, 95% confidence interval: 0.740-0.932, = 0.00155, adjust = 0.0311) exhibited a strong association with Alzheimer's disease-related dementia.
The results suggest that gut microbiota is causally associated with dementia. Our findings provide novel insights into the pathophysiology of dementia and have important implications for its treatment and prevention.
现有证据表明，肠道微生物群是多种形式痴呆症的重要环境风险因素，包括阿尔茨海默病性痴呆、血管性痴呆以及其他分类于别处疾病中的痴呆症。然而，肠道微生物群与不同形式痴呆症或其亚型之间的确切因果关系仍不清楚。
使用孟德尔随机化（MR）分析研究肠道微生物群与痴呆症或其亚型之间的假定因果关系。
利用来自MiBioGen联盟的公开可用的肠道微生物群相关全基因组关联研究（GWAS）汇总数据以及来自芬兰基因组计划（FinnGen consortium）的痴呆症及其亚型的GWAS汇总统计数据，进行双向、两样本MR分析。根据MR的基本原理选择工具变量，并使用F统计量评估其强度。采用了五种MR方法，并对研究结果的稳健性进行了验证。为了考虑多重比较，我们应用Bonferroni方法进行P值调整。
我们确定了几种与痴呆症或其亚型表现出假定因果关系的肠道微生物分类群，它们可能是该疾病的风险或保护因素。此外，反向MR分析表明，几种肠道微生物分类群的相对丰度可能受痴呆症或其亚型的影响。全面的敏感性分析证实不存在异质性和水平多效性。在应用多重检验校正后，我们观察到芽孢杆菌目（优势比：0.830，95%置信区间：0.740 - 0.932，P = 0.00155，调整后P = 0.0311）与阿尔茨海默病相关痴呆症有很强的关联。
结果表明肠道微生物群与痴呆症存在因果关联。我们的研究结果为痴呆症的病理生理学提供了新的见解，并对其治疗和预防具有重要意义。
