Metabonomic Variation of Exopolysaccharide from Rhizopus nigricans on AOM/DSS-Induced Colorectal Cancer in Mice

BACKGROUND: Colorectal cancer (CRC), which occurs at the junction of the rectum and sigmoid colon, is a common malignancy associated with poor prognosis and high mortality worldwide. The exopolysaccharide (EPS1-1), isolated from the fermentation broth of Rhizopus nigricans (R. nigricans), has been reported to possess anti-CRC properties. However, the metabolic alterations caused by azoxymethane (AOM) and dextran sulfate sodium (DSS) are still unknown. METHODS: In the present study, a mice colon cancer model was established by treatment with AOM/DSS. LC-MS/MS-based metabolomics studies were performed to analyze metabolic alterations at the tissue level. Partial least squares discriminant analysis (PLS-DA) was used to identify differentially expressed metabolites. RESULTS: Nineteen distinct metabolites were identified that were associated with disruptions in the following pathways: biosynthesis of unsaturated fatty acids, pyrimidine metabolism, phenylalanine metabolism, fatty acid metabolism, folate biosynthesis, and inositol phosphate metabolism. Furthermore, six significantly altered metabolites were involved in these six pathways. Compared with the Model group, the expression of cytosine, deoxyuridine, 20-hydroxy-leukotriene E4, and L-homocysteic acid was lower, whereas that of 2-dehydro-3-deoxy-6-phospho-D-gluconic acid and hematoporphyrin was higher in the EPS1-1 group. CONCLUSION: The results of multivariate statistical analysis demonstrate a promising application of the above metabolites by EPS1-1 in CRC therapy. Deeper understanding of the related mechanism warrants further investigation.