ACCORDING TO 2013 DATA FROM THE GLOBAL HEALTH ORGANISATION, CARDIOMETABOLICAS DISEASES ARE THE LEADING CAUSE OF DEATH WORLDWIDE AND ADD A HUGE BURDEN TO SOCIETY, BOTH THROUGH THE LOSS OF QUALITY OF LIFE AND HEALTH AND IN SPENDING THE RESOURCES OF THE HEALTH SYSTEM. THE CLINICAL MANAGEMENT OF THESE DISEASES IS VERY COMPLEX BECAUSE THEY CAN BE PRESENT FOR YEARS BEFORE BECOMING CLINICALLY APPARENT. UNDERSTANDING OF THEIR PATHOGENESIS AND RELATED DISEASES HAS BECOME INCREASINGLY IMPORTANT. THE DEVELOPMENT OF SPECIFIC BIOMARKERS FOR THE EARLY DETECTION OF CARDIOMETABOLICA DISEASE AND TO CHARACTERISE NEW SUBGROUPS OF PATIENTS LIKELY TO RESPOND TO SPECIFIC THERAPIES SEEMS FUNDAMENTAL IN RISK MANAGEMENT AND PATIENT MANAGEMENT. HOST-METABOLISM-INTESTINAL MICROBIOTA APPEARS TO BE INVOLVED IN THE PROGRESSION OF THE DISEASE. ALTHOUGH MODULATION OF THE MICROBIOTA HAS BEEN POSTULATED AS A VERY EFFECTIVE THERAPEUTIC APPROACH, IT IS NOT CLEAR WHETHER ALL PATIENTS CAN BENEFIT FROM IT AND WHAT MARKERS CAN PREDICT THE SUCCESS OF THIS TYPE OF THERAPY. OUR GROUP HAS SHOWN IN PREVIOUS STUDIES THAT: 1) PART OF THIS CO-METABOLISM CAN BE DETECTED IN PATIENTS BOTH IN BLOOD AND URINE AND 2) ALTERATIONS OF THE METABOLITES INVOLVED APPEAR IN RATS BEFORE CLINICAL MANIFESTATION OF THE DISEASE. THE STUDY OF THE SEQUENCE OF EVENTS IN THESE ALTERATIONS CAN BE USED FOR THE BENEFIT OF THE PATIENT BOTH FOR EARLY DETECTION AND FOR THE CHARACTERISATION OF THE DISEASE AND THE DESIGN OF NEW THERAPIES. THE GENERAL OBJECTIVE OF THE PROJECT IS TO OBTAIN NEW MARKERS, NEW SUBGROUPS AND NEW PREVENTIVE AND THERAPEUTIC APPROACHES IN CARDIOMETABOLICAL DISEASE BASED ON THE CHARACTERISATION AND MODULATION OF HOST-MICROBIOTA-INTESTINAL CO-METABOLISM. TO DO THIS, WE WILL CONDUCT A LONGITUDINAL STUDY OF METABOLOMICA AND ANALYSIS OF FAECAL MICROBIOTA IN GROUPS OF RATS UNDERGOING DIFFERENT INTERVENTIONS, INCLUDING RICH DIET IN FRUCTOSE AND FAT, TREATMENT WITH SYMBIOTICS AND INTESTINAL MICROBIOTA TRANSPLANTS. MOLECULAR CHARACTERISATION OF THE DISEASE THROUGH METABOLOMIC, PYROSEQUENCE OF FAECAL DNA, INFLAMMATION MARKERS AND GENIC EXPRESSION PROFILES WILL HELP TO BETTER UNDERSTAND THE UNDERLYING MECHANISMS. A COMMON CARDIOMETABOLICA CHARACTERISATION PROTOCOL WILL ALLOW BETTER COMPARISON OF RESULTS IN RATS AND HUMANS. THE VALIDATION OF PROFILES AND MARKERS IN TWO HUMAN COHORTS (ONE OF THE GENERAL POPULATION AND THE OTHER OF CASES-CONTROLS) WILL GUIDE THE TRANSLATION OF THE RESULTS TO THE CLINICAL PRACTICE. WE HOPE TO BUILD AND CONTRIBUTE TO DIAGNOSTIC AND PREDICTIVE MATHEMATICAL MODELS BASED ON HOST-MICROBIOTA-INTESTINAL CO-METABOLISM DETERMINED BY MRI. THIS IS A CHEAP, REPRODUCIBLE AND DIRECT APPROACH WITH APPLICATION TO GENERAL POPULATION AND POSSIBLE SCREENING PROGRAMS. THE RESULTS OF THE PROJECT CAN HELP IN THE NEAR FUTURE FOR A BETTER CHARACTERISATION, TREATMENT SELECTION AND OVERALL MANAGEMENT OF THE PATIENT WITH CARDIOMETABOLICAL DISEASE.
