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早期肠道微生物群筛查能否降低认知障碍的发生率?一项孟德尔随机研究。

Can early gut microbiota screening reduce the incidence of cognitive impairment? A Mendelian randomization study.

机构信息

Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.

出版信息

J Alzheimers Dis. 2024 Nov;102(1):195-206. doi: 10.3233/JAD-231457. Epub 2024 Oct 23.

DOI:10.3233/JAD-231457
PMID:39497320
Abstract

Gastrointestinal symptoms are now detected early in the clinical course of many dementia patients, and studies of the microbiome-gut-brain axis have confirmed bidirectional interactions between the gut and the brain. However, the causal relationship between gut microbiota and cognitive impairment has not been fully established. Therefore, this study conducted a bidirectional Mendelian randomization study to elucidate the potential causal relationship of gut microbiota to cognitive impairment. Using Mendelian randomization to identify gut flora with a genetic causal effect on the development of cognitive impairment. This study utilized publicly available genome-wide association study summary data to perform MR analysis, with gut microbiota as the exposure and various cognitive function indicators as well as scores for Alzheimer's disease as outcomes. This study selected single nucleotide polymorphisms as instrumental variables based on p-values, F-statistics, and r. Bidirectional Mendelian randomization was conducted using methods such as inverse variance weighted, MR-Egger, simple mode, and weighted mode to assess the causal relationship. Concurrently, this study carried out Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis to identify potential heterogeneity and horizontal pleiotropy. This study identified a total of 31 gut microbes that have a causal relationship with cognitive impairment, which include 1 phylum, 4 classes, 3 orders, 2 families, and 21 genera. This study unveiled specific gut microbiota associated with cognitive impairment, offering new insights and approaches for the prevention and treatment of cognitive impairment through gut microbiota such as Bifidobacterium and Ruminococcus gnavus group.

摘要

胃肠道症状现在在许多痴呆症患者的临床病程早期被检测到,并且微生物组-肠道-大脑轴的研究已经证实了肠道和大脑之间的双向相互作用。然而,肠道微生物群与认知障碍之间的因果关系尚未完全确立。因此,本研究进行了双向孟德尔随机化研究,以阐明肠道微生物群与认知障碍之间的潜在因果关系。使用孟德尔随机化来确定具有遗传因果作用的肠道菌群对认知障碍发展的影响。本研究利用公开的全基因组关联研究汇总数据进行 MR 分析,将肠道菌群作为暴露因素,将各种认知功能指标以及阿尔茨海默病评分作为结果。本研究基于 p 值、F 统计量和 r 值选择单核苷酸多态性作为工具变量。使用逆方差加权、MR-Egger、简单模式和加权模式等方法进行双向孟德尔随机化,以评估因果关系。同时,本研究进行了 Cochran's Q 检验、MR-Egger 截距检验和逐一剔除分析,以识别潜在的异质性和水平多效性。本研究总共确定了 31 种与认知障碍有因果关系的肠道微生物,包括 1 个门、4 个纲、3 个目、2 个科和 21 个属。本研究揭示了与认知障碍相关的特定肠道微生物群,为通过双歧杆菌和真杆菌群等肠道微生物群预防和治疗认知障碍提供了新的见解和方法。

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