Obiettivo The clinical phenotype and the outcome of Crohn's disease (CD) and ulcerative colitis (UC), the opposite ends of chronic inflammatory bowel diseases (IBD), are heterogeneous and represent the result of a complex interplay of the gut microbiome with the immune system in genetically predisposed individuals. Disease management is much less heterogeneous as all patients are treated using non-specific anti-inflammatory agents, and only 30-50% achieve clinical and mucosal remission -the goal of therapy nowadays- therefore leaving large margins for improvement. The advances in knowledge about the factors triggering disease onset should be translated to approach the disease from a molecular angle. Key cellular pathways have emerged including bacterial recognition, autophagy, endoplasmic reticulum stress and intestinal barrier function. Functional/molecular characterization of these pathways in a given patient, correlation with meaningful clinical outcomes, and tailoring an individual therapeutic approach has never been attempted and will represent a breakthrough in the current paradigm of treating multifactorial inflammatory conditions. This project aims to functionally characterize patients with CD/UC for the major pathways by using integrated (epi)genetic, transcriptomic, immunologic, barrier integrity and metagenomic studies. From these readouts we will construct an index [the Crohn’s and Ulcerative Colitis Characterization and Intervention trial (CrUCCial) index], reflecting the proportional contribution of each of the pathogenic mechanisms in a given patient. We will next study the correlation of this index and its components to meaningful clinical outcomes and finally, the index will be tested in a pilot study of newly diagnosed patients in whom the disease will be targeted individually based on the components of the CrUCCial index. Our approach, from diagnosis over prognosis to therapy, will revolutionize the paradigm of disease management. Campo scientifico medical and health sciencesclinical medicinegastroenterologyinflammatory bowel diseasemedical and health sciencesbasic medicineimmunology Parole chiave Inflammatory Bowel diseases Crohn's disease ulcerative colitis immune-mediated inflammatory disorders dysbiosis intestinal barrier Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-ADG-2015 - ERC Advanced Grant Invito a presentare proposte ERC-2015-AdG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-ADG - Advanced Grant Istituzione ospitante KATHOLIEKE UNIVERSITEIT LEUVEN Contribution nette de l'UE € 2 494 500,00 Indirizzo OUDE MARKT 13 3000 Leuven Belgio Mostra sulla mappa Regione Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 494 500,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto KATHOLIEKE UNIVERSITEIT LEUVEN Belgio Contribution nette de l'UE € 2 494 500,00 Indirizzo OUDE MARKT 13 3000 Leuven Mostra sulla mappa Regione Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven Tipo di attività Higher or Secondary Education Establishments Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 494 500,00