Exploring the relationship between APOEε4 allele and gut microbiota composition and function in healthy adults

Abstract The APOE ε4 allele (APOE4) is a known risk factor for neurodegenerative and cardiovascular diseases, but its link to body composition and metabolism remains debated. The gut microbiota influences host metabolism and immunity, yet its relationship with APOE genotype in healthy individuals is...

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Main Authors: C. Bressa, R. González-Soltero, M. Tabone, S. Clemente-Velasco, B. G. Gálvez, M. Larrosa
Format: Article
Language:English
Published: SpringerOpen 2025-05-01
Series:AMB Express
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Online Access:https://doi.org/10.1186/s13568-025-01888-4
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author C. Bressa
R. González-Soltero
M. Tabone
S. Clemente-Velasco
B. G. Gálvez
M. Larrosa
author_facet C. Bressa
R. González-Soltero
M. Tabone
S. Clemente-Velasco
B. G. Gálvez
M. Larrosa
author_sort C. Bressa
collection DOAJ
description Abstract The APOE ε4 allele (APOE4) is a known risk factor for neurodegenerative and cardiovascular diseases, but its link to body composition and metabolism remains debated. The gut microbiota influences host metabolism and immunity, yet its relationship with APOE genotype in healthy individuals is not well understood. The objective of this work was to examine associations between APOE genotype and gut microbiota composition and function in healthy adults, focusing on microbial and metabolic differences related to the APOE4 allele. Seventy-seven healthy Spanish adults were genotyped for APOE. Fecal microbiota profiles were assessed by 16 S rRNA gene sequencing, and predicted functions were inferred using PICRUSt2. Body composition (DEXA) and physical activity (accelerometry) were also measured. APOE4 carriers exhibited subtle shifts in microbiota composition, including a five-fold reduction in Megamonas and lower abundance of the Eubacterium brachy group—both linked to energy harvest and adiposity—compared to APOE3 homozygotes. An uncharacterized Puniceicoccaceae genus was enriched in APOE4 carriers. Although E. brachy group abundance correlated with adiposity, no significant differences in body composition were observed. Functional predictions showed APOE4-associated microbiota enriched in pathways for carotenoid biosynthesis and trehalose metabolism, and depleted in tryptophan biosynthesis, propionate production, and multidrug resistance mechanisms. APOE4 carriers harbor gut microbiota with distinct taxonomic and functional features, potentially reflecting adaptations to metabolic and oxidative challenges. These findings underscore the relevance of the gut microbiome in shaping APOE4-associated phenotypes and warrant further investigation into its mechanistic contributions to health and disease.
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spelling doaj-art-e9934d1906924f93b95bef46bc098db32025-08-20T02:25:17ZengSpringerOpenAMB Express2191-08552025-05-0115111310.1186/s13568-025-01888-4Exploring the relationship between APOEε4 allele and gut microbiota composition and function in healthy adultsC. Bressa0R. González-Soltero1M. Tabone2S. Clemente-Velasco3B. G. Gálvez4M. Larrosa5Masmicrobiota Research GroupMasmicrobiota Research GroupMasmicrobiota Research GroupMasmicrobiota Research GroupMasmicrobiota Research GroupMasmicrobiota Research GroupAbstract The APOE ε4 allele (APOE4) is a known risk factor for neurodegenerative and cardiovascular diseases, but its link to body composition and metabolism remains debated. The gut microbiota influences host metabolism and immunity, yet its relationship with APOE genotype in healthy individuals is not well understood. The objective of this work was to examine associations between APOE genotype and gut microbiota composition and function in healthy adults, focusing on microbial and metabolic differences related to the APOE4 allele. Seventy-seven healthy Spanish adults were genotyped for APOE. Fecal microbiota profiles were assessed by 16 S rRNA gene sequencing, and predicted functions were inferred using PICRUSt2. Body composition (DEXA) and physical activity (accelerometry) were also measured. APOE4 carriers exhibited subtle shifts in microbiota composition, including a five-fold reduction in Megamonas and lower abundance of the Eubacterium brachy group—both linked to energy harvest and adiposity—compared to APOE3 homozygotes. An uncharacterized Puniceicoccaceae genus was enriched in APOE4 carriers. Although E. brachy group abundance correlated with adiposity, no significant differences in body composition were observed. Functional predictions showed APOE4-associated microbiota enriched in pathways for carotenoid biosynthesis and trehalose metabolism, and depleted in tryptophan biosynthesis, propionate production, and multidrug resistance mechanisms. APOE4 carriers harbor gut microbiota with distinct taxonomic and functional features, potentially reflecting adaptations to metabolic and oxidative challenges. These findings underscore the relevance of the gut microbiome in shaping APOE4-associated phenotypes and warrant further investigation into its mechanistic contributions to health and disease.https://doi.org/10.1186/s13568-025-01888-4APOEε4 alleleGut microbiotaMetabolic functionHealthy adultsBody composition
spellingShingle C. Bressa
R. González-Soltero
M. Tabone
S. Clemente-Velasco
B. G. Gálvez
M. Larrosa
Exploring the relationship between APOEε4 allele and gut microbiota composition and function in healthy adults
AMB Express
APOEε4 allele
Gut microbiota
Metabolic function
Healthy adults
Body composition
title Exploring the relationship between APOEε4 allele and gut microbiota composition and function in healthy adults
title_full Exploring the relationship between APOEε4 allele and gut microbiota composition and function in healthy adults
title_fullStr Exploring the relationship between APOEε4 allele and gut microbiota composition and function in healthy adults
title_full_unstemmed Exploring the relationship between APOEε4 allele and gut microbiota composition and function in healthy adults
title_short Exploring the relationship between APOEε4 allele and gut microbiota composition and function in healthy adults
title_sort exploring the relationship between apoeε4 allele and gut microbiota composition and function in healthy adults
topic APOEε4 allele
Gut microbiota
Metabolic function
Healthy adults
Body composition
url https://doi.org/10.1186/s13568-025-01888-4
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