MICROBIOTA CO-METABOLISM MODULATION AND EARLY DEVELOPMENT OF CARDIOMETABOLIC DISEASE ON HOST ORGANISM ANALYZED BASED ON METABOLOMICS AND PYROSEQUENCING

Abstract

Objective: Cardiometabolic disease (CMD) is a clustering of cardiometabolic risk factors of obesity, hypertension, fatty liver disease, type 2 diabetes and cardiovascular disease. This disorder that involve Host-microbiota co-metabolism and Western diets, with high-fat content is one of the main causes of mortality with fast increment nowadays. The study of metabolism involved and a development of specific biomarkers for early detection of cardiometabolic disease seems essential in patient management. The objective is to identify potential CMD biomarkers through analysis of changes involved in serum metabolism by NMR-metabolomics and microbiota modulation by DGGE and Pyrosequencing. Design and method: Male Wistar rats, 16 weeks old, were fed with a high-fat and sucrose diet (HFD) for 12 weeks to induce MS. Blood serum from high-fat fed rats was analyzed by Metabolomic analysis. This analysis was performed by Nuclear magnetic resonance (1H NMR) and microbiota diversity was observed in fecal samples by Denaturant gradient gel electrophoresis (DGGE) and Pyrosequencing. Results: HFD induced an increase in body weight, changes in glycemic levels and higher levels of arterial blood pressure and triglycerides and lower HDL levels in comparison with control rats. Liver histology revealed higher intra-hepatocytic lipid content, suggesting an early hepatic damage. The metabolomic profile of blood serum, demonstrated metabolism differences in HFD group that affected metabolites involved in different metabolic pathways. Moreover, host-microbiota co-metabolites were also altered. This analysis seems indicate a correlation between some microbial metabolites with cardiometabolic parameters. In addition, Pyrosequencing and DGGE studies revealed changes in the microbiota composition that this revealed lower microbiota diversity in the HFD group. Conclusions: Microbiota co-metabolism seems modulate the early development of CMD on host organism and the 1H NMR-based metabolomics can provide a non-invasive mean for MS early detection.