Descrizione del progetto
Quali informazioni provengono dal nostro intestino sulle malattie cardiovascolari?
Una quantità crescente di prove mette in evidenza l’abbinamento tra microbiota intestinale e malattie cardiovascolari. L’obiettivo generale del progetto GUTSY, finanziato dall’UE, è valutare i legami causali tra microbiota intestinale e malattia aterosclerotica, oltre a identificare i biomarcatori accessibili per il microbiota intestinale in grado di migliorare l’aterosclerosi. Il progetto definirà le caratteristiche del microbiota correlate all’aterosclerosi avvalendosi di tomografia computerizzata coronarica, angiografia ed ecografia ad alta risoluzione della carotide, in uno studio basato su una popolazione di 10 000 soggetti. Il microbiota sarà caratterizzato dal sequenziamento di nuova generazione di campioni fecali. I biomarcatori plasmatici correlati al microbiota che migliorano l’aterosclerosi saranno identificati mediante profilazione metabolomica e saranno condotte analisi genetiche per chiarire gli effetti causali delle caratteristiche del microbiota intestinale sulle malattie cardiovascolari.
Obiettivo
Atherosclerosis is the main pathological mechanism causing myocardial infarction and ischemic stroke. Evidence has mounted about the association between the gut microbiota and cardiovascular disease, but whether the associations are causal is largely unknown. For optimal prevention and treatment of cardiovascular disease, there is an urgent need to determine whether there are any true effects that might be targeted by interventions. The overall goal of this project is to assess causality between gut microbiota and atherosclerotic disease and to provide easily accessible biomarkers for an atherosclerosis-enhancing gut microbiota. To this end, the research program has three main objectives:
1.) Identification of gut microbiota characteristics associated with atherosclerosis measured by coronary computed tomography angiography and high-resolution carotid ultrasound in a population-based sample of 10,000 individuals and through prospective follow-up for myocardial infarction and ischemic stroke. The microbiota will be characterized by next-generation sequencing techniques in faecal samples.
2.) Identification of plasma biomarkers associated with an atherosclerosis- enhancing microbiota using comprehensive metabolomics profiling of 800 named metabolites in plasma from 800 individuals with replication in additional 800 individuals
3.) Clarification of the causal effects of gut microbiota characteristics on atherosclerosis, myocardial infarction and stroke by development of novel genetic instruments and applying Mendelian Randomization analysis
I have access to unique study materials and documented experience of successful projects using large scale -omics data and state-of-the-art epidemiological methodologies. My project is expected to lead to the identification of characteristics of an atherosclerosis-enhancing gut microbiota and associated plasma biomarkers that may open up new avenues for effective prevention of atherosclerotic disease.
Campo scientifico
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
751 05 Uppsala
Svezia