Phenotyping using Metabolomics for Nutritional Epidemiology – PhenoMeNEp

The purpose of dietary assessment is to estimate intake of foods, nutrients, bioactive compounds and food contaminants for exploration of associations with health outcomes and monitoring of population nutritional status. These data are still extremely difficult to obtain, especially at the individual level, due to the wide range of foods consumed and the high heterogeneity and variability of human dietary choices. Current methods based on questionnaires and a limited number of validated biomarkers of intake available are definitely not sufficient to assess dietary intakes with the accuracy and level of detail required for modern epidemiology. Evidence has mounting that much of the inconsistency of the results in nutritional epidemiology is largely due to poor dietary assessment.
This project aims at developing a new innovative and integrative approach, based on mass spectrometry metabolomics, to characterize dietary intake and nutritional status of populations. Progress in high-throughput analytical technologies and in bioinformatics now allows the simultaneous analysis of hundred(s) of low molecular weight metabolites present in biofluids or tissues and constituting the metabolome, including all metabolites directly coming from the digestion and metabolism of food components. This part of the metabolome, called the Food metabolome, encompass a huge diversity of food components that are absorbed in the gut. Any given plant food contains a few hundreds of phytochemicals from different chemical families, which when ingested with the food, are absorbed to various extent and transformed in the body by intestinal and hepatic enzymes, as well as by the microbiota, into a number of metabolites, some of them being still unidentified. Our hypothesis is that the comparison of the phytochemical part of the metabolome of individuals consuming or not a specific plant food or a F&V -rich diet should lead to the discovery of new biomarkers of intake for these foods and diets. The proposal builds on some preliminary results obtained with the Agruvasc project (ANR ALIA 2007-2009), in which we clearly discriminated urine metabolomes of subjects consuming Citrus juices, both as part of a fully controlled diet or with their regular diet. Several phytochemical metabolites reflecting citrus intake could be identified. Some were expected but most of them had not been recognized before and would have never been anticipated as putative biomarkers using a traditional approach.
PhenoMeNEp will be the first attempt worldwide to search biomarkers of food intake using metabolomics in a cohort study. Two subgroups of volunteers from the SU.VI.MAX2 cohort, with contrasted level of fruit and vegetable (F&V) intake as assessed by questionnaires (1st vs 5th quintile of intake) will be selected. Plasma and urine metabolomes will be explored to identify biomarkers reflecting the consumption of F&V-rich diet or of 11 specific plant foods selected for their interest in chronic disease prevention.
The metabolomic approach offers a considerable promise for dietary assessment; however progress is still hampered by several methodological problems, especially the difficulties met for annotating metabolites of phytochemicals. Primary objectives of the project will be to develop optimized MS-based analytical method and data mining workflow for the food metabolome, including a Food Metabolome database containing information on phytochemical metabolites. These developments are highly expected by the scientific community. They will make possible the full exploitation of the wealth of diet-relative information contained in the human metabolome.
The project will rely on the complementary competencies from UREN (Unité de Recherche en Epidémiologie Nutritionnelle U 557 Inserm/ U 1125 Inra / CNAM /Université Paris 13) and UNH (Unité de Nutrition Humaine UMR 1019- INRA Clermont-Theix/Univ. Auvergne), regarding epidemiology, phytochemical metabolism and metabolomics.