Nutritional metabolomics to assess exposure to plant food bioactives
The health effects of plant foods have been largely demonstrated and have led to general nutritional recommendations in many countries. However many questions remain: What are the most protective compounds or associations of compounds? Are some foods more protective than others? What is the extent of inter-individual variation in response to plant foods intake and what are the determinants (age, gender, genotype, microbiota composition…) involved in this variation? To take these questions into consideration in controlled intervention and observational studies it is essential to properly assess the exposure of individuals to the wide range of metabolites derived from plant food consumption. Plant foods typically contains hundreds of phytochemicals that are absorbed to various extent and can be metabolized by intestinal and hepatic enzymes as well as by the microbiota. Many metabolites are still not known. Traditional dietary assessment methods based on dietary questionnaires and table of food composition do not offer the accuracy and coverage required for plant food bioactive metabolites. In recent years, non-targeted metabolomics based on high resolution mass-spectrometry made possible the holistic exploration of the food-derived metabolites present in biofluids, defined as the Food metabolome. This approach opened tremendous opportunities, in particular for dietary assessment and investigation of inter-individual variation in the field of plant food bioactives. Significant efforts are currently being made, in the framework of international collaborations, for the development of the food metabolome approach, with new tools and methods to facilitate identification of unknowns in metabolomic profiles.
Current research focus
Development of tools and methods for the exploration of the Food metabolome
In collaboration with the INRA Platform for Metabolic Exploration (PFEM) we are developing tools and methods for the analysis of the phytochemical part of the Food metabolome using high-resolution mass spectrometry. A major achievement was the online database PhytoHub (http://phytohub.eu/), launched in September 2014. PhytoHub is the first database focused on dietary phytochemicals (~1500 compounds) and their human metabolites and was designed for use in metabolomics. PhytoHub is regularly updated with the contribution of experts for the different families of compounds.
In the framework of the European project JPI Foodball, we are contributing in collaboration with the group of D. Wishart in Canada to the development of new resources to facilitate identification of unknowns in metabolomic profiles: a web portal dedicated to the Food metabolome (www.foodmetabolome.org), FoodComEx (www.foodcomex.org), an international chemical library for non easily available food-derived compounds, and an in silico tool for prediction of non-nutrient metabolism.
- Discovery and validation of biomarkers of plant food intake and of dietary patterns
- Search of associations between comprehensive profiles of exposure to plant food bioactive metabolites and health outcomes (cardiovascular disease risks, cognitive function, breast cancer) in controlled intervention and cohort studies
- Interindividual variation in bioavailability and metabolism of plant food bioactives. Relative impact of age, gender, genotype and microbiota composition.
- Valorisation of tropical fruits
Recent and ongoing projects
-DCogPlast project JPI HDHL (2016-2018, 1.1 M€, 6 partners). Untargeted metabolomics in the 3C cohort to discover dietary biomarkers and bioactives associated with accelerated or preserved cognitive decline and brain plasticity.
- Foodball project JPI HDHL (2015-2017, 4.38M€, 22 partners). The Food biomarker alliance. Systematic exploration and validation of dietary biomarkers to improve the quality of dietary assessment. Leader of WP "Development of tools and ressources for food metabolomics and dietary biomarker discovery".
- COST Action POSITIVe FA 1403 (2015-2018, 71 partners, 31 countries). Interindividual variation in response to plant food bioactives and determinants involved. Co-leader WG "Interindividual variation in bioavailability". Leader of the Metabolomics group.
- MetaboKS project, INCA (2014-2017, 362k€, 6 partners). Discovery of new biomarkers to improve breast cancer risk prediction: new insights from metabolomics applied to nutritional epidemiology. Leader of task "New biomarkers of the quality of usual diet (adherence to nutritional recommendations)".
- PhenoMeNEp Project ANR-ALIA (2011-2013, 366k€, 3 partners). "Phenotyping using metabolomics for nutritional epidemiology". Project coordinator. Identification of a new plant food intake biomarkers by untargeted profiling of SU.VI.MAX2 subjects.
- 7th International Conference on Polyphenols and Health, Tours, France, 27-30th Oct 2015.
- 1st International workshop of the COST Action POSITIVe, Tours, France, 26-27th Oct 2015.
- 1st International workshop “Food metabolome and biomarkers for dietary exposure”, Glasgow, UK, July 2013.
- 2nd International Congress of Translational Research in Human Nutrition, Clermont-Ferrand, France, March 2013.
- www.phytohub.eu : online Database dedicated to food phytochemicals and their human metabolite
- www.foodcomex.org : chemical library for rare food-derived compounds
- Rothwell, J. A.; Fillâtre, Y.; Martin, J. F.; Lyan, B.; Pujos-Guillot, E.; Fezeu, L.; Hercberg, S.; Comte, B.; Galan, P.; Touvier, M.; Manach, C., New biomarkers of coffee consumption identified by the non-targeted metabolomic profiling of cohort study subjects Plos One 2014, 9, (4), e93474.
- Scalbert, A.; Brennan, L.; Manach, C.; Andres-Lacueva, C.; Dragsted, L. O.; Draper, J.; Rappaport, S.; Van der Hooft, J.; Wishart, D., The food metabolome: a window over dietary exposure. Am J Clin Nutr 2014, 99(6): 1286-1308.
- Manach C, Brennan L and Dragsted L (2014). Metabolomics to evaluate food intake and utilization in nutritional epidemiology. In: Metabolomics as a tool in nutritional research. Edited by Sebedio J, Brennan L. pp. 167-196, Woodhead publishing.
- Pujos-Guillot, E.; Hubert, J.; Martin, J. F.; Lyan, B.; Quintana, M.; Claude, S.; Chabanas, B.; Rothwell, J. A.; Bennetau-Pelissero, C.; Scalbert, A.; Comte, B.; Hercberg, S.; Morand, C.; Galan, P.; Manach, C., Mass Spectrometry-based Metabolomics for the Discovery of Biomarkers of Fruit and Vegetable Intake: Citrus Fruit as a Case Study. Journal of Proteome Research 2013, 12, (4), 1645-1659.
- Manach, C., Hubert, J., Llorach, R. & Scalbert, A. (2009) The Complex Links Between Dietary Phytochemicals and Human Health Deciphered by Metabolomics. Molecular Nutrition & Food Research 53: 1303-1315.