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APOE genetics influence murine gut microbiome.

Diana J Zajac1, Stefan J Green2,3, Lance A Johnson1

  • 1Department of Physiology and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.

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|February 4, 2022
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Summary
This summary is machine-generated.

Apolipoprotein E (APOE) alleles significantly alter gut microbiome composition in male mice, with specific bacterial changes linked to APOE2 and APOE4 variants. These findings, including increased Erysipelotrichia with APOE4, were observed in humans, suggesting a potential mechanism for APOE

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Area of Science:

  • Microbiology
  • Genetics
  • Human Health

Background:

  • Apolipoprotein E (APOE) alleles are linked to various human diseases and have shown associations with the gut microbiome.
  • Understanding the precise relationship between APOE alleles and the gut microbiome is crucial for disease prevention and treatment strategies.

Purpose of the Study:

  • To investigate the impact of APOE heterozygosity on the gut microbiome in mice under controlled conditions.
  • To determine if APOE allelic status influences microbial diversity and composition.
  • To explore potential sex-specific differences in APOE's effect on the microbiome and validate findings in human data.

Main Methods:

  • Utilized APOE targeted replacement (TR) mice modeling human APOE alleles (APOE2, APOE3, APOE4).
  • Maintained mice under homogenous environmental conditions to minimize variability.
  • Analyzed fecal microbiota using 16S ribosomal RNA gene amplicon sequencing at multiple time points.
  • Employed LefSe, cladograms, alpha/beta diversity analyses, and univariate statistics to identify APOE-associated taxa and patterns.
  • Compared mouse findings with published human microbiome genome-wide association data.

Main Results:

  • Robust differences in gut microbiome composition were observed in male mice associated with APOE status, with limited differences in females.
  • Alpha and beta diversity of the fecal microbiome were significantly associated with APOE status in males but not females.
  • A stepwise pattern of microbial changes was identified, with APOE2 associated with increased Clostridia/Ruminococcaceae and APOE4 with increased Erysipelotrichia.
  • The increase in Erysipelotrichia with APOE4 status in mice was replicated in human data.
  • Heterozygous APOE genotypes showed intermediate microbial profiles.

Conclusions:

  • Gut microbiome profiles are strongly associated with APOE status in male mice, particularly under controlled environmental conditions.
  • The observed increase in Erysipelotrichia with APOE4 in mice is conserved in humans, suggesting a shared biological mechanism.
  • APOE allelic effects on the microbiome appear intermediate in heterozygous individuals.
  • Further research is needed to elucidate the impact of APOE-associated microbiota on disease phenotypes in humans.