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

Tam T. T. Tran, Simone Corsini, Lee Kellingray, Claire Hegarty, Gwénaëlle Le Gall, Arjan Narbad, Michael Müller, Noemi Tejera, Paul W. O'Toole, Anne-Marie Minihane, David Vauzour

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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
Original languageEnglish
Pages (from-to)8221-8231
Number of pages11
JournalThe FASEB Journal
Issue number7
Early online date8 Apr 2019
Publication statusPublished - Jul 2019


  • apolipoprotein E
  • gut microbiota
  • metabolomics
  • butyrate
  • SCFAs

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