Jea Woo Kang, Lora A. Khatib, Margo B. Heston, Amanda H. Dilmore, Jennifer S. Labus, Yuetiva Deming, Leyla Schimmel, Colette Blach, Daniel McDonald, Antonio Gonzalez, MacKenzie Bryant, Tyler K. Ulland, Sterling C. Johnson, Sanjay Asthana, Cynthia M. Carlsson, Nathaniel A. Chin, Kaj Blennow, Henrik Zetterberg, Federico E. Rey, Alzheimer Gut Microbiome Project Consortium, Rima Kaddurah-Daouk, Rob Knight, Barbara B. Bendlin
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Bendlin","doi":"10.1002/alz.70417","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> BACKGROUND</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Gut microbiome composition and function differ between people with Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals.</li>\n \n <li>Co-occurring gut microbes show differential abundance across AD-related groups (AD vs CU, amyloid status+ vs amyloid status−, and apolipoprotein E (<i>APOE</i>) ε4 status+ vs <i>APOE</i> ε4 status−).</li>\n \n <li>Gut microbiome composition also differs between people with AD dementia and CU individuals in a larger validation cohort.</li>\n \n <li>Differentially abundant gut microbiome composition and function between AD and CU groups are correlated with cerebrospinal fluid biomarkers for AD and related pathologies.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 7","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70417","citationCount":"0","resultStr":"{\"title\":\"Gut microbiome compositional and functional features associate with Alzheimer's disease pathology\",\"authors\":\"Jea Woo Kang, Lora A. 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引用次数: 0
摘要
肠道微生物群是阿尔茨海默病（AD）的一个潜在可改变的危险因素；然而，对其组成和功能在AD病理中的理解是有限的。方法利用临床数据和脑脊液（CSF）生物标志物，利用浅枪霰弹枪宏基因组学分析阿尔茨海默病风险研究中威斯康星微生物组参与者的粪便微生物组。差异丰度和普通最小二乘回归分析发现差异丰富的肠道微生物组特征及其与阿尔茨海默病脑脊液生物标志物和相关病理的关联。结果：AD痴呆患者和非AD痴呆患者的肠道微生物组成和功能存在差异。组成差异在一个独立队列中得到了重复。差异丰富的肠道微生物特征与阿尔茨海默病的脑脊液生物标志物和相关病理有关。这些发现增强了我们对阿尔茨海默病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途径与阿尔茨海默病病理有关。肠道微生物组成和功能在阿尔茨海默病（AD）痴呆患者和认知未受损（CU）个体之间存在差异。共同发生的肠道微生物在AD相关组（AD vs CU，淀粉样蛋白状态+ vs淀粉样蛋白状态-，载脂蛋白E (APOE) ε4状态+ vs APOE ε4状态-）中表现出不同的丰度。在一个更大的验证队列中，AD痴呆患者和CU个体之间的肠道微生物组成也存在差异。AD组和CU组之间肠道微生物组成和功能的差异与AD和相关病理的脑脊液生物标志物相关。
Gut microbiome compositional and functional features associate with Alzheimer's disease pathology
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.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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