Periodic Reporting for period 2 - PREDICT-CARE (Developing tools for the PREDICTion, at individual level, of the CArdiometabolic REsponse to the consumption of dietary (poly)phenols)
Período documentado: 2022-07-01 hasta 2023-12-31
Cardiometabolic diseases represent the leading causes of death worldwide. Plant-based diets and phenolic-rich foods have been considered of pivotal importance in the prevention of these diseases, but the evidence on the protective role of dietary (poly)phenols in cardiometabolic health is not consistent yet. Inter-individual differences in the bioavailability and physiological response to the consumption of these compounds could condition their efficacy in promoting well-being. The PREDICT-CARE project aims to go deeper into the comprehension of individual’s capacity to metabolize dietary (poly)phenols and their effects on cardiometabolic health, assuming that differences among individuals in the production of phenolic metabolites may explain the differential cardiometabolic response to the consumption of (poly)phenols. The project intends to unravel the determinants driving responsiveness to (poly)phenols, allowing to predict their health benefits at individual level using translatable approaches. To reach this major goal, PREDICT-CARE foresees to: 1) identify aggregate metabolic phenotypes for the main dietary (poly)phenols and assess the factors associated with their formation by means of a standardized challenge test, 2) demonstrate the association between aggregate phenolic metabotypes and cardiometabolic health in response to the chronic intake of (poly)phenols, by linking specific metabotypes in the production of phenolic metabolites to changes in main cardiometabolic outcomes, and 3) develop an integrative analytical platform to identify individual phenolic metabotypes and to predict cardiometabolic responses to the consumption of dietary (poly)phenols, favoring an effective, feasible translation and implementation of the knowledge gained. The results of the project will open the door for future and more effective nutritional interventions based on the phenolic metabotype of each individual and his/her own singularities.
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.
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.
The novelty of the project relies on the application of a comprehensive approach in the prediction of the cardiometabolic response to the consumption of dietary (poly)phenols, taking into account inter-individual variability in both metabolism and health effects of these plant food bioactives, as well as the determinants behind it, whereas previous studies only focused on the assessment of metabotypes for single phenolic sub-classes generally on a small number of subjects. Said so, the expected results of the project are the identification of aggregate metabolic phenotypes for the main dietary (poly)phenols and the assessment of the factors associated with their formation, and the demonstration of the association between aggregate phenolic metabotypes and cardiometabolic health in response to the chronic intake of (poly)phenols. The identification of aggregate metabolic phenotypes for the main dietary (poly)phenols may be the key for the development of a new strategy to predict cardiometabolic response to (poly)phenol consumption through a high-throughput screening and prediction platform, by providing just little information on each individual’s makeup characteristics and a single urine sample. This achievement will boost nutrition at personalized level and guide the development of plant-based, cost-effective strategies for the promotion of cardiometabolic health.