APOE4 genotype shapes the role of dietary fibers in cognitive health through gut microbiota changes

Liaquat, Marrium, Le Gall, Gwenaelle, Scholey, Andrew, Pontifex, Matthew G., Bastiaanssen, Thomaz F. S., Muller, Michael, Minihane, Anne Marie and Vauzour, David (2025) APOE4 genotype shapes the role of dietary fibers in cognitive health through gut microbiota changes. Gut Microbes, 17 (1). ISSN 1949-0976

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Abstract

APOE4, a key risk factor for Alzheimer’s disease, influences gut microbiota and microbial metabolites (e.g. amino acids and dietary fiber (DF) derived short-chain fatty acids (SCFAs)). However, its role in modulating microbiota-driven DF metabolism and its effect on cognitive status remains unclear. This cross-sectional study (n = 170) investigates the association between APOE4 genotype, DF consumption, and metabolism in individuals with subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) compared to healthy controls (HC). Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) and 1H NMR metabolomic techniques were used to quantify SCFAs in serum and fecal samples, respectively. Gut microbiota speciation was carried out by 16S rRNA amplicon sequencing. We found that DF intake was significantly associated with APOE4 genotype and cognitive status, with lower consumption in APOE4 carriers (p < 0.05) and those with cognitive impairment (SCI and MCI) (p = 0.03). Differences (p < 0.05) in gut microbiota (both α- and β-diversity) and SCFAs were evident between APOE4 and non-APOE4 carriers, with stronger associations with DF consumption and cognitive status evident in non-APOE4 carriers. These findings suggest that targeting DF-induced changes in gut microbiota and serum SCFAs may be an effective strategy for mitigating cognitive impairment, but primarily in non-APOE4 carriers.

Item Type:	Article
Additional Information:	Data availability statement: The 16S rRNA gene sequence data have been deposited in the NCBI BioProject database (https://www.ncbi.nlm.nih.gov/bioproject/.) under accession number PRJNA1109848 (https://dataview.ncbi.nlm.nih.gov/object/PRJNA1109848?reviewer=6ap0u8gbeurjsalfs5141rrcvn). Other data that support the findings of this study are available from the corresponding authors upon reasonable request. Funding: This research work is part of Marrium Liaquat’s PhD which is funded by the Commonwealth Scholarship Commission and the Foreign, Commonwealth and Development Office in the UK. We are grateful for their support. All views expressed here are those of the authors not the funding body
Uncontrolled Keywords:	apoe genotype,cognitive status,short-chain fatty acids,microbiome,sci,mci,sdg 3 - good health and well-being,4* ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Medicine and Health Sciences > School of Health Sciences
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health
Related URLs:	https://www.tandfonline.com/doi/full/10....
Depositing User:	LivePure Connector
Date Deposited:	02 Jul 2025 14:30
Last Modified:	02 Jul 2025 14:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/99813
DOI:	10.1080/19490976.2025.2526133

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