Diet, fecal microbiome, and trimethylamine N-oxide in a cohort of metabolically healthy United States adults

Authors: JAMES, KRISTEN - University Of California, Davis; Gertz, Erik; CERVANTES, EDUARDO - University Of California, Davis; BONNEL, ELLEN - University Of California, Davis; Stephensen, Charles; Kable, Mary; Bennett, Brian

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/24/2022
Publication Date: 3/25/2022
Citation: James, K.L., Gertz, E.R., Cervantes, E., Bonnel, E., Stephensen, C.B., Kable, M.E., Bennett, B.J. 2022. Diet, fecal microbiome, and trimethylamine N-oxide in a cohort of metabolically healthy United States adults. Nutrients. 14(7). Article 1376. https://doi.org/10.3390/nu14071376.
DOI: https://doi.org/10.3390/nu14071376

Interpretive Summary: The objectives of our study are to characterize the levels of TMAO in a metabolically healthy cohort of adults living in the United States and to relate these levels to recent diet intake and the fecal microbiome to understand the drivers of TMAO variation. We relate TMAO to cardiometabolic risk factors to assess TMAO's biological role in healthy individuals. Notably, our study utilizes data from a cross-sectional study equally stratified by sex, age, and BMI allowing us to probe how these characteristics affect our outcomes.

Technical Abstract: TMAO is elevated in individuals with cardiometabolic diseases, but it is unknown whether the metabolite is a biomarker of concern in healthy individuals. We conducted a cross-sectional study in metabolically healthy adults ages 18-66 years and BMI 18-44 kg/m2 and assessed the relationship between TMAO and diet, the fecal microbiome, and cardiometabolic risk factors. TMAO was measured in fasted plasma samples by liquid chromatography mass spectrometry. The fecal microbiome was assessed by 16S ribosomal RNA sequencing and recent food intake was captured by multiple ASA24 dietary recalls. Endothelial function was assessed via EndoPAT. TMAO levels were not associated with average intake of animal protein foods, fruits, vegetables, dairy, or grains. TMAO was related to the fecal microbiome and genera Butyribrio, Roseburia, Coprobaciullus and Catenibacterium were enriched in individuals in the lowest versus the highest TMAO tertile. TMAO was positively associated with '-diversity and compositional differences were identified between groups. TMAO was not associated with classic cardiovascular risk factors in the health cohort. Similarly, endothelial function was not related to fasting TMAO whereas, the inflammatory marker TNF-' was significantly associated. Fasting plasma TMAO may not be a metabolite of concern in generally healthy adults unmedicated for chronic disease. Prospective studies in healthy individuals are necessary.