Icon Legend

This session is not in your schedule.

This session is in your schedule. Click again to remove it.

Session: Personalizing Nutrition - Select Genetic, Epigenetic and Microbiome Interactions Influencing Diet and Diet-related Diseases (Oral 13)

(OR13-04-23) The Cecal Microbiome of Diversity Outbred Mice Is Regulated by Genetics, Diet, and Sex

Sunday, July 23, 2023

4:36 PM – 4:48 PM ET

Location: Constitution B

Presenting Author(s)

Kristen L. James, PhD (she/her/hers)

Postdoctoral Research Fellow
University of Colorado Anschutz Medical Campus
Denver, Colorado, United States

Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

Co-Author(s)

LE

Levi W. Evans, PhD

Research Associate - Nutritionist
USDA-ARS WHNRC
Davis, California, United States
NH

Nazmul Huda, PhD

University of California, Davis
Davis, California, United States
EG

Erik R. Gertz, MS

Chemist
USDA-ARS WHNRC
Davis, California, United States
HA

Hooman Allayee, PhD

Professor of Preventive Medicine
University of Southern California
Los Angeles, California, United States
BB

Brian Bennett, PhD

Research Leader
USDA Agricultural Research Service
Davis, CA, USA

Disclosure(s):

Kristen L. James, PhD: No relevant financial relationship(s) with ineligible companies to disclose.

Levi W. Evans, PhD: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: Genetic variants have been demonstrated to influence the composition of the gut microbiome, nutritional requirements, and metabolic health, but how these factors interact remains underexplored. To address this, we investigated the genetic regulation of the cecal microbiome in Diversity Outbred (DO) mice and assessed whether the regulation is dependent on diet and sex.

Methods: The cecal microbiome was evaluated by 16S rRNA sequencing from DO mice (n=384) who were fed a purified diet (AIN-76A) for two weeks, followed by randomization to continue on AIN-76A or switched to AIN-76A supplemented with a high choline content (HC, 1.1% total choline) for two additional weeks. To identify compositional differences of the cecal microbiome by diet and sex, alpha and beta-diversity analyses were performed on rarefied data. Microbiome quantitative trait locus (mQTL) analysis was conducted to evaluate the genetic regulation of cecal microbiome traits and to evaluate the effects of diet and sex. Microbiome traits included quantile normalized amplicon sequence variants (ASVs) present in 20% of samples, agglomerated taxa at each phylogenetic level, alpha-diversity values, and the first three principal coordinate axes calculated from the beta-diversity analysis.

Results: The HC diet and female sex were related to reduced alpha-diversity (Shannon, β_HCdiet = -0.20, PHCdiet < 0.001; β_MaleSex = 0.23, PMaleSex < 0.001). Beta-diversity statistics also indicated a significant effect of diet and sex on the composition of the cecal microbiome (Weighted UniFrac, Pdiet < 0.001, Psex < 0.001; Unweighted UniFrac, Pdiet < 0.001, Psex < 0.001). Mice on the HC diet had a significantly reduced Firmicutes to Bacteroidetes ratio of 3.2 ± 1.5, compared to 4.5 ± 4.0 from mice on the AIN-76A diet (P < 0.001). Cecal microbiome composition was also associated with numerous loci throughout the genome, including regions that were dependent on diet or sex.

Conclusions: The composition of the murine cecal microbiome was impacted by both diet and sex. These factors also influenced the genetic regulation of microbiome traits and can be leveraged to advance the field of precision nutrition and reduce diet-mediated chronic disease.

Funding Sources: This work was funded by the USDA, Agricultural Research Service (2032-51530-025-00D), and the National Institute of Health (RO1HL148110).