Cited by 137Gut microbiota and healthNutritional Studies and DietNutrition, Genetics, and Disease

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Interplay between diet and gut microbiome, and circulating concentrations of trimethylamine N-oxide: findings from a longitudinal cohort of US men

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Li, Jun, Li, Yanping, Ivey, Kerry L, Wang, Dong D, Wilkinson, Jeremy E, Franke, Adrian, Lee, Kyu Ha, Chan, Andrew, Huttenhower, Curtis, Hu, Frank B, Rimm, Eric B, Sun, Qi·2022·Gut

DOI 10.1136/gutjnl-2020-322473PMC PMC8553812

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Abstract

Objectives: Gut-produced trimethylamine N-oxide (TMAO) is postulated as a possible link between red meat intake and poor cardiometabolic health. We investigated whether gut microbiome could modify associations of dietary precursors with TMAO concentrations and cardiometabolic risk markers among free-living individuals. Design: We collected up to two pairs of faecal samples (n=925) and two blood samples (n=473), 6 months apart, from 307 healthy men in the Men’s Lifestyle Validation Study. Diet was assessed repeatedly using food-frequency questionnaires and diet records. We profiled faecal metagenome and metatranscriptome using shotgun sequencing and identified microbial taxonomic and functional features. Results: TMAO concentrations were associated with the overall microbial compositions (permutational analysis of variance (PERMANOVA) test p=0.001). Multivariable taxa-wide association analysis identified 10 bacterial species whose abundance was significantly associated with plasma TMAO concentrations (false discovery rate <0.05). Higher habitual intake of red meat and choline was significantly associated with higher TMAO concentrations among participants who were microbial TMAO-producers (p<0.05), as characterised based on four abundant TMAO-predicting species, but not among other participants (for red meat , P-interaction =0.003; for choline, P-interaction =0.03). Among abundant TMAO-predicting species, Alistipes shahii significantly strengthened the positive association between red meat intake and HbA1c levels ( P-interaction =0.01). Secondary analyses revealed that some functional features, including choline trimethylamine-lyase activating enzymes, were associated with TMAO concentrations. Conclusion: We identified microbial taxa that were associated with TMAO concentrations and modified the associations of red meat intake with TMAO concentrations and cardiometabolic risk markers. Our data underscore the interplay between diet and gut microbiome in producing potentially bioactive metabolites that may modulate cardiometabolic health.

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Authors: Li, J., Li, Y., Ivey, K. L., Wang, D. D., Wilkinson, J. E., Franke, A., Lee, K. H., Chan, A., Huttenhower, C., Hu, F. B., Rimm, E. B., & Sun, Q.
Affiliations: Harvard University (US)
Brigham and Women's Hospital (US)
University of Hawaii Cancer Center (US)
Broad Institute (US)
Corresponding author: Sun, Qi
ORCID: Li, Jun
Li, Yanping
Ivey, Kerry L
Wang, Dong D
Wilkinson, Jeremy E
Franke, Adrian
Lee, Kyu Ha
Chan, Andrew
Huttenhower, Curtis
Hu, Frank B
Rimm, Eric B
Sun, Qi
Venue: Gut
Publisher: BMJ
Published: 2021-04-29
Volume: 71
Issue: 4
Pages: 724-733
ISSN: 0017-5749 (ISSN-L)
1468-3288
DOI: 10.1136/gutjnl-2020-322473
PMC: PMC8553812
OpenAlex: W3159306868
Cited by: 137
References: 41
Citations by year: 2026: 19 · 2025: 28 · 2024: 44 · 2023: 24 · 2022: 14 · 2021: 6
FWCI: 6.95
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Gut (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Heart, Lung, and Blood Institute (R01HL035464, R01HL060712, R01HL35464)
National Institute of Diabetes and Digestive and Kidney Diseases (K99DK122128, R01DK119268, R01DK120870, R01DK126698)
National Cancer Institute (U01CA152904, U01CA167552)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
Keywords: trimethylamine N-oxide, gut microbiota, red meat consumption, choline, cardiometabolic risk, HbA1c, Alistipes shahii, dietary precursors, microbial metabolites, men's health
MeSH terms: Gastrointestinal Microbiome, Cardiovascular Diseases, Choline, Diet, Humans, Male, Methylamines

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Interplay between diet and gut microbiome, and circulating concentrations of trimethylamine N-oxide: findings from a longitudinal cohort of US men

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