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

Author:

Kang Jea Woo,Khatib Lora A.,Heston Margo B.ORCID,Dilmore Amanda H.,Labus Jennifer S.,Deming YuetivaORCID,Schimmel Leyla,Blach Colette,McDonald Daniel,Gonzalez Antonio,Bryant MacKenzie,Sanders Karenina,Schwartz Lara,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.

Abstract

AbstractBACKGROUNDThe gut microbiome is a potentially modifiable factor in Alzheimer’s disease (AD); however, understanding of its composition and function regarding AD pathology is limited.METHODSShallow-shotgun metagenomic data was used to analyze fecal microbiome from participants enrolled 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.RESULTSGut microbiome composition and function differed between people with AD and cognitively unimpaired individuals. The compositional difference was replicated in an independent cohort. Differentially abundant gut microbiome features were associated with CSF biomarkers of AD and related pathologies.DISCUSSIONThese 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.

Publisher

Cold Spring Harbor Laboratory

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