We developed a dietary challenge test (so-called oral (poly)phenol challenge test, OPCT) to assess the metabolism of dietary (poly)phenols by each individual, aiming at identifying aggregate metabolic phenotypes for the main dietary (poly)phenols and assessing the factors associated with their formation. The OPCT is a single-dose acute clinical trial that consists in the administration of 3 tablets providing a standardized amount of different (poly)phenols, mimicking the habitual intake of these compounds, as reported for the European population. For the OPCT, 300 volunteer were recruited in one year. Anthropometric data and information on dietary and lifestyle habits (smoking, sleeping, and physical activity level), as well as blood pressure and heart rate were collected. Key data on genetic polymorphisms related to the metabolism of (poly)phenols, gut microbiota profile, biomarkers of cardiometabolic health, and cardiometabolic risk scores were gathered through the collection of urine, blood and stool samples. Urine samples were also analyzed for the evaluation of individual urinary excretion of phenolic metabolites, to unravel the aggregate phenolic metabotypes. In this sense, spot urine samples collected before and 24h after the challenge test were analyzed via an integrative analytical platform (consisting of an ultra-performance liquid chromatography system coupled to a high resolution mass spectrometer equipped with ion mobility separation (UPLC-IMS-QTOF-MS) and to a triple quadrupole mass spectrometer (UHPLC-QqQ-MS)), using an analytical method that allows a comprehensive identification and quantification of phenolic metabolites, specifically developed and validated for the project. Univariate and multivariate statistics will then be applied to define aggregate metabolic phenotypes for the main dietary (poly)phenols and assess the factors associated with their formation.
Preliminary results on a subset of almost 200 volunteers showed two aggregate metabotypes when applying different clustering methods. The two metabotypes were distinguished by a different metabolic rate (faster vs. slower metabolizers) and most discriminant metabolites were those of colonic origin. This implies the influence of the individual gut microbiota in the observed differences. Integration of metabolomics, microbiomics and genetic data from the OPCT study is currently ongoing.
The information collected has been key to design the second study, a chronic, randomized, control trial focused on cardiometabolic health and characterized by the presence of two aggregate phenolic metabotypes that will be further divided into a control diet or a personalized, (poly)phenol-rich diet.
Interdisciplinary collaborations of the PI have been developed and consolidated during this initial period. Moreover, a PhD student and some research fellows have been enrolled, demonstrating that the project can strongly support training and initial stage of career of future independent researchers.
