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Cited by 233Gut microbiota and healthAlzheimer's disease research and treatmentsOral microbiology and periodontitis research

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

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Tran, Tam T. T., Corsini, Simone, Kellingray, Lee, Hegarty, Claire, Le Gall, Gwénaëlle, Narbad, Arjan, Müller, Michael, Tejera, Noemi +3 more·2019·The FASEB Journal
DOI 10.1096/fj.201900071rPMC PMC6593891

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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 of APOE genotype on microflora speciation and metabolism is 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 gut microbiota of APOE ‐TR mice. Furthermore, metabolomic analysis of murine fecal water 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.—Tran, T. T. T., Corsini, S., Kellingray, L., Hegarty, C., Le Gall, G., Narbad, A., Müller, M., Tejera, N., O'Toole, P. W., Minihane, A.‐M., Vauzour, D . APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer's disease pathophysiology. FASEB J. 33, 8221–8231 (2019). www.fasebj.org

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Authors
Tran, T. T. T., Corsini, S., Kellingray, L., Hegarty, C., Le Gall, G., Narbad, A., Müller, M., Tejera, N., O'Toole, P. W., Minihane, A.-M., & Vauzour, D.
Affiliations
  • University College Cork (IE)
  • University of East Anglia (GB)
  • Norwich Research Park (GB)
  • Quadram Institute Bioscience Norwich Research Park Norwich United Kingdom
  • Norwich Medical School University of East Anglia Norwich United Kingdom
  • Alimentary Pharmabiotic Centre (APC) Microbiome Ireland University College Cork Cork Ireland
Corresponding author
Vauzour, David
ORCID
Venue
The FASEB Journal
Publisher
Wiley
Published
2019-04-08
Volume
33
Issue
7
Pages
8221-8231
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
DOI
10.1096/fj.201900071r
PMC
PMC6593891
OpenAlex
W2937882491
Cited by
233
References
76
Citations by year
2026: 27 · 2025: 42 · 2024: 34 · 2023: 37 · 2022: 40 · 2021: 26 · 2020: 20 · 2019: 7
FWCI
7.69
Type
journal article
Language
en
Open access
Licence
Locations
  • The FASEB Journal (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UEA Digital Repository (University of East Anglia) (acceptedVersion)
Funders
  • Biotechnology and Biological Sciences Research Council (BB/M004449/1)
  • Science Foundation Ireland
  • Association for Progressive Communications
  • Food Institutional Research Measure
  • Department of Agriculture, Food and the Marine, Ireland
  • Sugar Research Australia (PRJNA533610)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
Keywords
APOE genotype, apolipoprotein E, Alzheimer's disease, gut microbiota, Prevotellaceae, Ruminococcaceae, butyrate-producing bacteria, short-chain fatty acids, microbial metabolites, APOE ε4, cognitive decline, fecal microbiota
MeSH terms
Gastrointestinal Microbiome, Aged, Alzheimer Disease, Animals, Apolipoproteins E, Female, Genotype, Humans, Male, Mice, Transgenic, Middle Aged, Retrospective Studies, Butyric Acid, Mice, Cognitive Dysfunction

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