Identifying biomarkers of dietary patterns by using metabolomics

Abstract

Background: Healthy dietary patterns that conform to national dietary guidelines are related to lower chronic disease incidence and longer life span. However, the precise mechanisms involved are unclear. Identifying biomarkers of dietary patterns may provide tools to validate diet quality measurement and determine underlying metabolic pathways influenced by diet quality.

Objective: The objective of this study was to examine the correlation of 4 diet quality indexes [the Healthy Eating Index (HEI) 2010, the Alternate Mediterranean Diet Score (aMED), the WHO Healthy Diet Indicator (HDI), and the Baltic Sea Diet (BSD)] with serum metabolites.

Design: We evaluated dietary patterns and metabolites in male Finnish smokers (n = 1336) from 5 nested case-control studies within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Participants completed a validated food-frequency questionnaire and provided a fasting serum sample before study randomization (1985-1988). Metabolites were measured with the use of mass spectrometry. We analyzed cross-sectional partial correlations of 1316 metabolites with 4 diet quality indexes, adjusting for age, body mass index, smoking, energy intake, education, and physical activity. We pooled estimates across studies with the use of fixed-effects meta-analysis with Bonferroni correction for multiple comparisons, and conducted metabolic pathway analyses.

Results: The HEI-2010, aMED, HDI, and BSD were associated with 23, 46, 23, and 33 metabolites, respectively (17, 21, 11, and 10 metabolites, respectively, were chemically identified; r-range: -0.30 to 0.20; P = 6 × 10^-15 to 8 × 10^-6). Food-based diet indexes (HEI-2010, aMED, and BSD) were associated with metabolites correlated with most components used to score adherence (e.g., fruit, vegetables, whole grains, fish, and unsaturated fat). HDI correlated with metabolites related to polyunsaturated fat and fiber components, but not other macro- or micronutrients (e.g., percentages of protein and cholesterol). The lysolipid and food and plant xenobiotic pathways were most strongly associated with diet quality.

Conclusions: Diet quality, measured by healthy diet indexes, is associated with serum metabolites, with the specific metabolite profile of each diet index related to the diet components used to score adherence. This trial was registered at clinicaltrials.gov as NCT00342992.

Keywords: Healthy Eating Index; biomarker; diet quality; dietary pattern; metabolite; metabolomics.

FIGURE 1

Metabolic subpathways and proportion of total measured metabolites within each pathway associated with diet quality indexes in 1336 men in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. All pathways were statistically significantly associated with diet indexes at a Bonferroni significance level (P < 0.05/(46 × 4) = 2.7 × 10⁻⁴). Pathways are defined according to KEGG PATHWAY metabolism subpathways for Homo sapiens (http://www.genome.jp/kegg/pathway.html). Analyses were conducted with the use of multivariate linear regression with fixed-effects meta-analysis (Fisher’s method). The total number of metabolites measured by the Metabolon platform within each metabolic subpathway from highest to lowest were as follows: lysolipid (79); fatty acid, dicarboxylate (27); food component or plant (25); tocopherol (25); tryptophan (25); benzoate (18); chemical (16); carnitine (15); urea cycle (14); histidine (12); drug (11); pentose (10); essential PUFAs (7); long-chain PUFAs (7).