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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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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A longitudinal study on healthy men identified ten gut microbial species associated with plasma TMAO concentration.
“a longitudinal study conducted on healthy men has identified ten gut microbial species that are associated with plasma TMAO concentration.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [678]
Bacteroidetes Alistipes shahii significantly strengthened the association between red meat/choline intake and plasma TMAO levels.
“the Bacteroidetes Alistipes shahii significantly strengthened the association between red meat/choline intake and plasma TMAO levels.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [678]
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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
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2021-04-29
- Volume
- 71
- Issue
- 4
- Pages
- 724-733
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- 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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