APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer’s disease pathophysiology

Tran, Tam T. T., Corsini, Simone, Kellingray, Lee, Hegarty, Claire, Le Gall, Gwénaëlle, Narbad, Arjan, Müller, Michael, Tejera, Noemi, O'Toole, Paul W., Minihane, Anne-Marie and Vauzour, David (2019) APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer’s disease pathophysiology. The FASEB Journal, 33 (7). pp. 8221-8231. ISSN 0892-6638

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Abstract

Apolipoprotein E (APOE) genotype is the strongest prevalent genetic risk factor for Alzheimer’s disease (AD). Numerous studies have provided insights into the pathologic mechanisms. However, a comprehensive understanding of the impact ofAPOEgenotype onmicroflora speciation and metabolismis completely lacking. In this study,we investigated the association between APOE genotype and the gut microbiome composition in human and APOE–targeted replacement (TR) transgenic mice. Fecal microbiota amplicon sequencing from matched individuals with different APOE genotypes revealed no significant differences in overall microbiota diversity in group aggregated human APOE genotypes. However, several bacterial taxa showed significantly different relative abundance between APOE genotypes. Notably, we detected an association of Prevotellaceae and Ruminococcaceae and several butyrate-producing genera abundances with APOE genotypes. These findings were confirmed by comparing the gutmicrobiota ofAPOE-TRmice. Furthermore, metabolomic analysis of murine fecalwater detected significant differences in microbe-associated amino acids and short-chain fatty acids between APOE genotypes. Together, these findings indicate that APOE genotype is associated with specific gut microbiome profiles in both humans and APOE-TR mice. This suggests that the gut microbiome is worth further investigation as a potential target to mitigate the deleterious impact of the APOE4 allele on cognitive decline and the prevention of AD

Item Type: Article
Uncontrolled Keywords: apolipoprotein e,gut microbiota,metabolomics,butyrate,scfas
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Pharmacy
Faculty of Science > School of Biological Sciences
Depositing User: LivePure Connector
Date Deposited: 25 Apr 2019 15:30
Last Modified: 31 May 2020 23:47
URI: https://ueaeprints.uea.ac.uk/id/eprint/70707
DOI: 10.1096/fj.201900071R

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