Metabolomic profile of the Healthy Eating Index-2015 in the Multi-Ethnic Study of Atherosclerosis

Authors: GADGIL, MEGHANA - University Of California San Francisco (UCSF); WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); KARAMAN, IBRAHIM - Imperial College; GRACA, GONCALO - Imperial College; TZOULAKI, IOANNA - Imperial College; ZHONG, VICTOR - Shanghai Jiaotong University; GREENLAND, PHILIP - Northwestern University; KANAYA, ALKA - University Of California San Francisco (UCSF); HERRINGTON, DAVID - Wake Forest School Of Medicine

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/31/2023
Publication Date: 6/2/2023
Citation: Gadgil, M.D., Wood, A.C., Karaman, I., Graca, G., Tzoulaki, I., Zhong, V.W., Greenland, P., Kanaya, A.M., Herrington, D.M. 2023. Metabolomic profile of the Healthy Eating Index-2015 in the Multi-Ethnic Study of Atherosclerosis. Journal of Nutrition. https://doi.org/10.1016/j.tjnut.2023.05.030.
DOI: https://doi.org/10.1016/j.tjnut.2023.05.030

Interpretive Summary: Poor diet quality is a risk factor for type 2 diabetes and cardiovascular disease. However, the molecular mechanisms conveying protection from disease are poorly understood. Metabolomic data may help in this respect. Metabolites in the plasma reflect, in part, dietary intake, and therefore capture the physiological effects of food in our body. In this study, researchers examined which metabolites were associated with the Healthy Eating Index-2015, which measures adherence to the USDA's Dietary Guidelines for Americans (DGA). Higher HEI-2015 scores were associated with 4 discrete metabolites, which included amino acids and fatty acids. If future analysis clarifies the roles these metabolites play in the prevention of chronic disease, this study may present an important step in understanding how to use diet to protect health.

Technical Abstract: Poor diet quality is a risk factor for type 2 diabetes and cardiovascular disease. However, knowledge of metabolites marking adherence to Dietary Guidelines for Americans (2015 version; DGA-15) are limited. The goal was to determine a pattern of metabolites associated with the Healthy Eating Index-2015 (HEI-2015), which measures adherence to the DGA. The analysis examined 3557 adult men and women from the longitudinal cohort Multi-Ethnic Study of Atherosclerosis (MESA), without known cardiovascular disease and with complete dietary data. Fasting serum specimens, diet and demographic questionnaires were assessed at baseline. Untargeted 1H NMR 1DNMR spectroscopy (600 MHz) was used to generate metabolomics and lipidomics. A metabolome-wide association study (MWAS) specified each spectral feature as outcomes, HEI-2015 score as predictor, adjusting for age, gender, race, and study site in linear regression analyses. Subsequently, hierarchical clustering defined discrete groups of correlated NMR features associated with named metabolites and linear regression analysis assessed for associations with HEI-2015 total and component scores. The sample included 50% women with average age of 63 years, with 40% identifying as White, 23% Black, 24% Hispanic and 13% Chinese American. The average HEI-2015 score was 66. MWAS identified 179 spectral features significantly associated with HEI-2015 score. Cluster analysis identified seven clusters representing 4 metabolites; HEI-2015 score was significantly associated with all. HEI-2015 score was associated with proline betaine (Beta 0.12 [0.02]; p=4.70 E-13) and was inversely related to proline (Beta -0.13 [0.02]; p=4.45 E-14), 1,5 anhydrosorbitol (Beta -0.08 [0.02]; p=4.37 E-07) and unsaturated fatty acyl chains (Beta 0.08 [0.02]; p=8.98 E-07). Intake of total fruit, whole grains and seafood and plant proteins was associated with proline betaine. Diet quality was significantly associated with unsaturated fatty acyl chains, proline betaine, proline. Further analysis may clarify the link between diet quality, metabolites, and pathogenesis of cardiometabolic disease.