肠道微生物群的组成和功能特征与阿尔茨海默病病理学相关。

Gut microbiome compositional and functional features associate with Alzheimer's disease pathology.

作者信息

Kang Jea Woo, Khatib Lora A, Heston Margo B, Dilmore Amanda H, Labus Jennifer S, Deming Yuetiva, Schimmel Leyla, Blach Colette, McDonald Daniel, Gonzalez Antonio, Bryant MacKenzie, Ulland Tyler K, Johnson Sterling C, Asthana Sanjay, Carlsson Cynthia M, Chin Nathaniel A, Blennow Kaj, Zetterberg Henrik, Rey Federico E, Kaddurah-Daouk Rima, Knight Rob, Bendlin Barbara B

机构信息

Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Department of Pediatrics, University of California, San Diego, La Jolla, California, USA.

出版信息

Alzheimers Dement. 2025 Jul;21(7):e70417. doi: 10.1002/alz.70417.

DOI:10.1002/alz.70417

PMID:40604345

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12221809/

Abstract

BACKGROUND

The gut microbiome is a potentially modifiable risk factor for Alzheimer's disease (AD); however, understanding of its composition and function regarding AD pathology is limited.

METHODS

Shallow-shotgun metagenomics was used to analyze the fecal microbiome of participants in the Wisconsin Microbiome in Alzheimer's Risk Study, leveraging clinical data and cerebrospinal fluid (CSF) biomarkers. Differential abundance and ordinary least squares regression analyses were performed to find differentially abundant gut microbiome features and their associations with CSF biomarkers of AD and related pathologies.

RESULTS

Gut microbiome composition and function differed between individuals with and without AD dementia. The compositional difference was replicated in an independent cohort. Differentially abundant gut microbiome features were associated with CSF biomarkers of AD and related pathologies.

DISCUSSION

These findings enhance our understanding of alterations in gut microbial composition and function in AD, and suggest that gut microbes and their pathways are linked to AD pathology.

HIGHLIGHTS

Gut microbiome composition and function differ between people with Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals. Co-occurring gut microbes show differential abundance across AD-related groups (AD vs CU, amyloid status+ vs amyloid status-, and apolipoprotein E (APOE) ε4 status+ vs APOE ε4 status-). Gut microbiome composition also differs between people with AD dementia and CU individuals in a larger validation cohort. Differentially abundant gut microbiome composition and function between AD and CU groups are correlated with cerebrospinal fluid biomarkers for AD and related pathologies.

摘要

背景

肠道微生物群是阿尔茨海默病（AD）一个潜在的可改变风险因素；然而，关于其在AD病理方面的组成和功能的了解有限。

方法

利用临床数据和脑脊液（CSF）生物标志物，采用浅鸟枪法宏基因组学分析威斯康星州阿尔茨海默病风险研究参与者的粪便微生物群。进行差异丰度分析和普通最小二乘回归分析，以发现差异丰富的肠道微生物群特征及其与AD及相关病理的CSF生物标志物的关联。

结果

患有和未患有AD痴呆症的个体之间肠道微生物群的组成和功能存在差异。这种组成差异在一个独立队列中得到了重复验证。差异丰富的肠道微生物群特征与AD及相关病理的CSF生物标志物相关。

讨论

这些发现增强了我们对AD中肠道微生物组成和功能改变的理解，并表明肠道微生物及其代谢途径与AD病理相关。

要点

患有阿尔茨海默病（AD）痴呆症的人和认知未受损（CU）个体之间肠道微生物群的组成和功能不同。同时出现的肠道微生物在AD相关组（AD与CU、淀粉样蛋白状态阳性与淀粉样蛋白状态阴性、载脂蛋白E（APOE）ε4状态阳性与APOEε4状态阴性）中显示出不同的丰度。在一个更大的验证队列中，患有AD痴呆症的人和CU个体之间的肠道微生物群组成也存在差异。AD组和CU组之间差异丰富的肠道微生物群组成和功能与AD及相关病理的脑脊液生物标志物相关。