Polyphenol metabolome in human urine and its association with intake of polyphenol-rich foods across European countries

Abstract

An improved understanding of the contribution of the diet to health and disease risks requires accurate assessments of dietary exposure in nutritional epidemiologic studies. The use of dietary biomarkers may improve the accuracy of estimates. We applied a metabolomic approach in a large cohort study to identify novel biomarkers of intake for a selection of polyphenol-containing foods. The large chemical diversity of polyphenols and their wide distribution over many foods make them ideal biomarker candidates for such foods. Metabolic profiles were measured with the use of high-resolution mass spectrometry in 24-h urine samples from 481 subjects from the large European Prospective Investigation on Cancer and Nutrition cohort. Peak intensities were correlated to acute and habitual dietary intakes of 6 polyphenol-rich foods (coffee, tea, red wine, citrus fruit, apples and pears, and chocolate products) measured with the use of 24-h dietary recalls and food-frequency questionnaires, respectively. Correlation (r > 0.3, P < 0.01 after correction for multiple testing) and discriminant [pcorr (1) > 0.3, VIP > 1.5] analyses showed that >2000 mass spectral features from urine metabolic profiles were significantly associated with the consumption of the 6 selected foods. More than 80 polyphenol metabolites associated with the consumption of the selected foods could be identified, and large differences in their concentrations reflecting individual food intakes were observed within and between 4 European countries. Receiver operating characteristic curves showed that 5 polyphenol metabolites, which are characteristic of 5 of the 6 selected foods, had a high predicting ability of food intake. Highly diverse food-derived metabolites (the so-called food metabolome) can be characterized in human biospecimens through this powerful metabolomic approach and screened to identify novel biomarkers for dietary exposures, which are ultimately essential to better understand the role of the diet in the cause of chronic diseases.