PP.07.11] SUBCLINICAL FRUCTOSE-INDUCED METABOLIC SYNDROME ASSOCIATED TO HOST-MICROBIOTA CO-METABOLISM IN RATS

Abstract

Objective: Metabolic syndrome (MS) is a rapidly growing worldwide pandemic, which is associated with a greater risk of multiple chronic pathologies including cardiovascular disease hypertension and Type 2 diabetes. Host-microbiota co-metabolism and Western diets, with high-fructose content, have been strongly implicated in the development of MS. The development of specific biomarkers for early detection of cardiometabolic disease seems essential in patient management. The aim of this study was to identify potential MS biomarkers to detect subclinical MS using a multi-approach combining 1H NMR-based metabolomics, microbiome analyses with MiSeq and liver histology. Urine, blood serum and fecal extracts from high- fructose fed rats were analyzed. Design and method: Male Wistar rats 4 weeks old were fed with a high-fructose (HF) diet (60%) for 15 weeks to induce MS. We applied high resolution NMR spectroscopy to profile serum, urine and fecal extracts. Principal component analysis (PCA) and projection to latent structures for discriminant analysis (PLS-DA) were applied to NMR spectral datasets. Results were cross-validated using the Venetian Blinds approach. Statistical analysis was performed using in-house MATLAB scripts and the PLS Toolbox statistical multivariate analysis library. Results: These HF rats exhibited insulin resistance and higher levels of systolic blood pressure and triglycerides and lower HDL levels than controls. Liver histology revealed higher intra-hepatocytic lipid content, suggesting an early hepatic damage. The metabolomic profile of blood serum, urine and fecal extracts demonstrated differences associated to HF diet. Metabolites affected are involved in glycolysis, glycogenesis, TCA cycle, amino acid degradation pathways, urea cycle and glycerophospholipids metabolism among others. Interestingly, host-microbiota co-metabolites were also altered. Microbiota composition revealed lower microbiota diversity in the HF group. Conclusions: 1H NMR-based metabolomics can provide a non-invasive mean for detection of sub-clinical organ damage and early MS. Microbiota co-metabolism by both diversity and functional composition seems to play a role in modulating the early development of MS on host organism.