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

(OR13-02-23) Probing Interactions Between Host Genetic Predisposition, Dietary Intake, and the Gut Microbiome

Sunday, July 23, 2023

4:12 PM – 4:24 PM ET

Location: Constitution B

Presenting Author(s)

Katia Chadaideh, PhD

Postdoctoral Research Fellow
Brigham and Women's Hospital, Harvard Medical School, Harvard T.H. Chan School of Public Health
Cambridge, Massachusetts, United States

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

Co-Author(s)

YL

Yuxi Liu

Harvard T.H. Chan School of Public Health
ZM

Zhendong Mei (he/him/his)

Postdoc fellow
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School
Jamaica Plain, Massachusetts, United States
RM

Raaj Mehta

Massachusetts General Hospital
AC

Andrew T. Chan, MD, MPH

Professor of Medicine
Massachusetts General Hospital and Harvard Medical School
Boston, Massachusetts, United States
WW

Walter c. Willett, DrPH, MPH, MD

Professor
Harvard T.H. Chan School of Public Health
Boston, Massachusetts, United States
ER

Eric B. Rimm, ScD

Professor
Harvard T.H. Chan School of Public Health
Boston, Massachusetts, United States
MS

Meir J. Stampfer, MD, PhD

Professor
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School
Boston, Massachusetts, United States
PK

Peter Kraft, PhD

Harvard T.H. Chan School of Public Health
Boston, Massachusetts, United States
CH

Curtis Huttenhower, PhD (he/him/his)

Professor
Harvard T.H. Chan School of Public Health
Boston, Massachusetts, United States
DW

Dong D. Wang, ScD

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School
Boston, Massachusetts, United States

Disclosure(s):

Katia Chadaideh, PhD: No relevant financial relationship(s) with ineligible companies to disclose.

Curtis Huttenhower, PhD: Seres Therapeutics: Advisory Committee/Board Member (Ongoing); Consultant (Ongoing); Stock Shareholder (excluding mutual funds) (Ongoing)
ZOE: Advisory Committee/Board Member (Ongoing)

Objectives: To investigate whether the association between host genetics and dietary intake varies by individuals’ gut microbial profiles.

Methods: We conducted this study in 470 men and women with dietary, host genetic, and gut microbiome data from Nurses’ Health Study II and Health Professionals Follow-Up Study. Long-term usual dietary intake was measured using food frequency questionnaires. Host genotypes were assayed using 5 genotyping arrays and imputed using the 1000 Genomes Project data. Whole-genome metagenomic sequencing was performed on fecal samples, and gut microbiome composition and function were profiled using the bioBakery3 workflow.

Results: In our gene-diet association models, we validated an inverse relationship between the G allele of rs4988235 in the lactase gene (LCT) and lactose intake (2.2 g/day lower per G allele [95% CI:0.6-3.8]), as well as a marginal positive relationship between the T allele of rs56113850 in CYP2A6 and caffeine intake (11.1 mg/day higher per T allele [95% CI:-9.9-32.0]). Our permutational multivariate analysis of variance found significant, albeit modest, impacts of LCT and CYP2A6 on gut microbial community structure, with each genotype explaining 0.4% of the total variance of species-level taxonomy. Coffee and dairy intakes were each significantly associated with the enrichment of several microbial species. In particular, we observed enrichment of the species Bifidobacterium longum associated with lactose intake (False discovery rate [FDR]=0.152 for lactose). We also found differentially abundant microbial functions in relation to diet intake, with the lactose and galactose degradation pathway enriched in those with higher lactose and nonfermented dairy intakes (FDR=0.249 for lactose; FDR=0.236 for nonfermented dairy). Finally, we determined strong interactions between genetics and microbiome features in diet intake. The inverse association between genetically inferred lactose intolerance and dairy intake was only apparent among individuals with lower abundance of B. longum (P_interaction=0.017 for lactose; 0.008 for nonfermented dairy).

Conclusions: Overall, our work highlights gene-microbiome interactions in diet behavior and suggests that the gut microbiome may modify the effects of genetic predisposition on dietary intake.

Funding Sources: NIH NRSA (T32), NIH Research Project Grant Program (R01)