Trimethylamine N-Oxide Response to a Mixed Macronutrient Tolerance Test in a Cohort of Healthy United States Adults

James, Kristen L.; Gertz, Erik R.; Kirschke, Catherine P.; Allayee, Hooman; Huang, Liping; Kable, Mary E.; Newman, John W.; Stephensen, Charles B.; Bennett, Brian J.

doi:10.3390/ijms24032074

Open AccessArticle

Trimethylamine N-Oxide Response to a Mixed Macronutrient Tolerance Test in a Cohort of Healthy United States Adults

by

Kristen L. James

¹

,

Erik R. Gertz

²,

Catherine P. Kirschke

²,

Hooman Allayee

^3,4,

Liping Huang

^1,2,

Mary E. Kable

^1,2

,

John W. Newman

^1,2

,

Charles B. Stephensen

^1,2 and

Brian J. Bennett

^1,2,*

¹

Department of Nutrition, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA

²

USDA-ARS Western Human Nutrition Research Center, 430 West Health Sciences Drive, Davis, CA 95616, USA

³

Department of Population & Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA

⁴

Department of Biochemistry & Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2023, 24(3), 2074; https://doi.org/10.3390/ijms24032074

Submission received: 7 December 2022 / Revised: 14 January 2023 / Accepted: 18 January 2023 / Published: 20 January 2023

(This article belongs to the Special Issue Gut Microbiota Derived Metabolites in Cardiovascular Health and Disease)

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Abstract

Plasma trimethylamine n-oxide (TMAO) concentration increases in responses to feeding TMAO, choline, phosphatidylcholine, L-carnitine, and betaine but it is unknown whether concentrations change following a mixed macronutrient tolerance test (MMTT) with limited amounts of TMAO precursors. In this proof-of-concept study, we provided healthy female and male adults (n = 97) ranging in age (18–65 years) and BMI (18–44 kg/m²) a MMTT (60% fat, 25% sucrose; 42% of a standard 2000 kilo calorie diet) and recorded their metabolic response at fasting and at 30 min, 3 h, and 6 h postprandially. We quantified total exposure to TMAO (AUC-TMAO) and classified individuals by the blood draw at which they experienced their maximal TMAO concentration (TMAO-response groups). We related AUC-TMAO to the 16S rRNA microbiome, to two SNPs in the exons of the FMO3 gene (rs2266782, G>A, p.Glu158Lys; and rs2266780, A>G, p.Glu308Gly), and to a priori plasma metabolites. We observed varying TMAO responses (timing and magnitude) and identified a sex by age interaction such that AUC-TMAO increased with age in females but not in males (p-value = 0.0112). Few relationships between AUC-TMAO and the fecal microbiome and FMO3 genotype were identified. We observed a strong correlation between AUC-TMAO and TNF-α that depended on TMAO-response group. These findings promote precision nutrition and have important ramifications for the eating behavior of adults who could benefit from reducing TMAO exposure, and for understanding factors that generate plasma TMAO.

Keywords: trimethylamine-n oxide; meal response; mixed macronutrient tolerance test; cardiovascular disease; gut microbiota; precision nutrition; phosphatidylcholine; bile acids; metabolomics; metabolites

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MDPI and ACS Style

James, K.L.; Gertz, E.R.; Kirschke, C.P.; Allayee, H.; Huang, L.; Kable, M.E.; Newman, J.W.; Stephensen, C.B.; Bennett, B.J. Trimethylamine N-Oxide Response to a Mixed Macronutrient Tolerance Test in a Cohort of Healthy United States Adults. Int. J. Mol. Sci. 2023, 24, 2074. https://doi.org/10.3390/ijms24032074

AMA Style

James KL, Gertz ER, Kirschke CP, Allayee H, Huang L, Kable ME, Newman JW, Stephensen CB, Bennett BJ. Trimethylamine N-Oxide Response to a Mixed Macronutrient Tolerance Test in a Cohort of Healthy United States Adults. International Journal of Molecular Sciences. 2023; 24(3):2074. https://doi.org/10.3390/ijms24032074

Chicago/Turabian Style

James, Kristen L., Erik R. Gertz, Catherine P. Kirschke, Hooman Allayee, Liping Huang, Mary E. Kable, John W. Newman, Charles B. Stephensen, and Brian J. Bennett. 2023. "Trimethylamine N-Oxide Response to a Mixed Macronutrient Tolerance Test in a Cohort of Healthy United States Adults" International Journal of Molecular Sciences 24, no. 3: 2074. https://doi.org/10.3390/ijms24032074

APA Style

James, K. L., Gertz, E. R., Kirschke, C. P., Allayee, H., Huang, L., Kable, M. E., Newman, J. W., Stephensen, C. B., & Bennett, B. J. (2023). Trimethylamine N-Oxide Response to a Mixed Macronutrient Tolerance Test in a Cohort of Healthy United States Adults. International Journal of Molecular Sciences, 24(3), 2074. https://doi.org/10.3390/ijms24032074

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Trimethylamine N-Oxide Response to a Mixed Macronutrient Tolerance Test in a Cohort of Healthy United States Adults

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