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Dietary factors, gut microbiota, and serum trimethylamine-N-oxide associated with cardiovascular disease in the Hispanic Community Health Study/Study of Latinos.

TitleDietary factors, gut microbiota, and serum trimethylamine-N-oxide associated with cardiovascular disease in the Hispanic Community Health Study/Study of Latinos.
Publication TypePublication
Year2021
AuthorsMei Z, Chen G-C, Wang Z, Usyk M, Yu B, Baeza YVazquez, Humphrey G, Benitez RSalido, Li J, Williams-Nguyen JS, Daviglus ML, Hou L, Cai J, Zheng Y, Knight R, Burk RD, Boerwinkle E, Kaplan RC, Qi Q
JournalAm J Clin Nutr
Volume113
Issue6
Pagination1503-1514
Date Published2021 06 01
ISSN1938-3207
KeywordsAdult, Aged, Biomarkers, Cardiovascular Diseases, Cross-Sectional Studies, diet, Female, Gastrointestinal Microbiome, Hispanic Americans, Humans, Male, Methylamines, Middle Aged, Public Health
Abstract

BACKGROUND: Trimethylamine-N-oxide (TMAO), a diet-derived and gut microbiota-related metabolite, is associated with cardiovascular disease (CVD). However, major dietary determinants and specific gut bacterial taxa related to TMAO remain to be identified in humans.OBJECTIVES: We aimed to identify dietary and gut microbial factors associated with circulating TMAO.METHODS: This cross-sectional study included 3972 participants (57.3% women) aged 18-74 y from the Hispanic Community Health Study/Study of Latinos in the United States. Dietary information was collected by 24-h dietary recalls at baseline interview (2008-2011), and baseline serum TMAO and its precursors were measured by an untargeted approach. Gut microbiome was profiled by shotgun metagenomic sequencing in a subset of participants (n = 626) during a follow-up visit (2016-2018). Logistic and linear regression were used to examine associations of inverse-normalized metabolites with prevalent CVD, dietary intake, and bacterial species, respectively, after adjustment for sociodemographic, behavioral, and clinical factors.RESULTS: TMAO was positively associated with prevalent CVD (case number = 279; OR = 1.34; 95% CI: 1.17, 1.54, per 1-SD). Fish (P = 1.26 × 10-17), red meat (P = 3.33 × 10-16), and egg (P = 3.89 × 10-5) intakes were top dietary factors positively associated with TMAO. We identified 9 gut bacterial species significantly associated with TMAO (false discovery rate <0.05). All 4 species positively associated with TMAO belong to the order Clostridiales, of which 3 might have homologous genes encoding carnitine monooxygenase, an enzyme converting carnitine to trimethylamine (TMA). The red meat-TMAO association was more pronounced in participants with higher abundances of these 4 species compared with those with lower abundance (Pinteraction = 0.013), but such microbial modification was not observed for fish-TMAO or egg-TMAO associations.CONCLUSION: In US Hispanics/Latinos, fish, red meat, and egg intakes are major dietary factors associated with serum TMAO. The identified potential TMA-producing gut microbiota and microbial modification on the red meat-TMAO association support microbial TMA production from dietary carnitine, whereas the fish-TMAO association is independent of gut microbiota.

DOI10.1093/ajcn/nqab001
Alternate JournalAm J Clin Nutr
PubMed ID33709132
PubMed Central IDPMC8168354
Grant ListR01 MD011389 / MD / NIMHD NIH HHS / United States
R01 DK119268 / DK / NIDDK NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
R01 HL140976 / HL / NHLBI NIH HHS / United States
R01 HL060712 / HL / NHLBI NIH HHS / United States
MS#: 
0971
Manuscript Lead/Corresponding Author Affiliation: 
Field Center: Bronx (Einstein College of Medicine)
ECI: 
Manuscript Affiliation: 
Field Center: Bronx (Einstein College of Medicine)
Manuscript Status: 
Published