The PREDICT-CARE project aims to develop integrative tools for predicting individual cardiometabolic responses to dietary (poly)phenols (PPs), bioactive compounds abundant in plant-based foods. Despite their known health benefits, PP bioavailability and physiological effects vary significantly among individuals. We aim to investigate inter-individual variability in PP metabolism and its implications for cardiometabolic (CM) health using a multi-omics approach, with a focus on genomics, to identify genetic variants and regulatory mechanisms, alongside complementary metabolomics and metagenomics analysis. We recruited 300 healthy volunteers (18–74 years) and collected data on diet, lifestyle, body composition, health status, and biological samples (blood, urine, feces). Participants underwent an oral (poly)phenol challenge test (OPCT) involving acute supplementation of multiple dietary PPs. Over 200 urinary metabolites were identified (by UPLC-IMS-HRMS) and quantified (by UPLC-QqQ-MS/MS), then analyzed using UMAP and k-means clustering to define metabolic phenotypes (metabotypes) distinguishing high and low PP producers. ITS sequencing on fecal samples characterized gut microbiome composition, revealing species associated with metabotypes. Genotyping (Illumina) followed by genotype imputation enabled the first GWAS on dietary PPs and CM traits, considering both binary (metabotype) and continuous (metabolite) phenotypes. GWAS and functional analyses highlighted novel genetic loci associated with PP metabolism. Significant associations emerged in genes related to PP ADME, such as the UGT1A complex, SULT, SULF, and ABC transporters. Three genomic loci (on chromosomes 14, 16, and 22), including the TSHR gene, were associated with PP traits. Gene set enrichment analyses suggested involvement of regulatory mechanisms such as gene dosage and epigenetic silencing. Integration with eQTL and chromatin interaction data revealed cis-regulatory architectures potentially modulating these loci.
How (poly)phenols can shape a healthier life? A nutri-omics investigation on their cardiometabolic health effects / Treccani, Mirko; Mignogna, Cristiana; Ghiretti, Lucia; Rinaldi De Alvarenga, Jose' Fernando; Favari, Claudia; Bragazzi, Nicola; Morandini, Maria Sole; Del Burgo Gutierrez, Cristina; Rosi, Alice; Negro, Cristiano; Bergamo, Federica; Bresciani, Letizia; Turroni, Francesca; Ventura, Marco; Dei Cas, Alessandra; Bonadonna, Riccardo; Barili, Valeria; Malerba, Giovanni; Del Rio, Daniele; Martorana, Davide; Mena, Pedro. - (2025). (Intervento presentato al convegno XXVIII Congresso Nazionale SIGU 2025 tenutosi a Rimini nel 23-25/09/2025).
How (poly)phenols can shape a healthier life? A nutri-omics investigation on their cardiometabolic health effects
Mirko Treccani
;Cristiana Mignogna;Lucia Ghiretti;Jose Fernando Rinaldi de Alvarenga;Claudia Favari;Nicola Bragazzi;Maria Sole Morandini;Cristina Del Burgo-Gutierrez;Alice Rosi;Cristiano Negro;Federica Bergamo;Letizia Bresciani;Francesca Turroni;Marco Ventura;Alessandra Dei Cas;Riccardo Bonadonna;Valeria Barili;Daniele Del Rio;Davide Martorana;Pedro Mena
2025-01-01
Abstract
The PREDICT-CARE project aims to develop integrative tools for predicting individual cardiometabolic responses to dietary (poly)phenols (PPs), bioactive compounds abundant in plant-based foods. Despite their known health benefits, PP bioavailability and physiological effects vary significantly among individuals. We aim to investigate inter-individual variability in PP metabolism and its implications for cardiometabolic (CM) health using a multi-omics approach, with a focus on genomics, to identify genetic variants and regulatory mechanisms, alongside complementary metabolomics and metagenomics analysis. We recruited 300 healthy volunteers (18–74 years) and collected data on diet, lifestyle, body composition, health status, and biological samples (blood, urine, feces). Participants underwent an oral (poly)phenol challenge test (OPCT) involving acute supplementation of multiple dietary PPs. Over 200 urinary metabolites were identified (by UPLC-IMS-HRMS) and quantified (by UPLC-QqQ-MS/MS), then analyzed using UMAP and k-means clustering to define metabolic phenotypes (metabotypes) distinguishing high and low PP producers. ITS sequencing on fecal samples characterized gut microbiome composition, revealing species associated with metabotypes. Genotyping (Illumina) followed by genotype imputation enabled the first GWAS on dietary PPs and CM traits, considering both binary (metabotype) and continuous (metabolite) phenotypes. GWAS and functional analyses highlighted novel genetic loci associated with PP metabolism. Significant associations emerged in genes related to PP ADME, such as the UGT1A complex, SULT, SULF, and ABC transporters. Three genomic loci (on chromosomes 14, 16, and 22), including the TSHR gene, were associated with PP traits. Gene set enrichment analyses suggested involvement of regulatory mechanisms such as gene dosage and epigenetic silencing. Integration with eQTL and chromatin interaction data revealed cis-regulatory architectures potentially modulating these loci.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
