Abstract 2343: Fecal metabolic changes following rice bran supplementation in the murine model for colitis associated cancer of the colon

Abstract

Abstract Dietary rice bran mediated inhibition of colon carcinogenesis has been described via multiple mechanisms including, but not limited to, reduced cell proliferation, induction of apoptosis and modulation of arachidonic acid metabolism. Human clinical research further supports rice bran modulation of gut microbiome metabolism for enhancing colonic health. Little is known regarding the time series of fecal metabolite changes involved in the progression of colon cancer in Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) treated mice and modulation of metabolic pathways by dietary rice bran supplementation. This study investigated the metabolic changes associated with rice bran supplementation during colitis-associated cancer over 14 weeks. Conventional adult male BALB/c mice were fed control diet (AIN93) or 10% w/w rice bran diet during AOM-DSS treatment. Global, non-targeted metabolomics was applied to murine fecal samples following consumption of rice bran after 2 days, 2, 6, 10 and 14 weeks and compared to mice fed control diet. Raw data was extracted, peak-identified and processed using Metabolon's hardware and software. A total of 702 biochemicals, 592 compounds of known identity and 110 compounds of unknown structural identity were reported, and ANOVA contrasts used to identify biochemicals that differed significantly between experimental groups. Random forest analysis based on an ensemble of decision trees revealed dietary distinctions in 30 metabolites at 10wk and 14wk with a predictive accuracy of 92% and 75%, respectively. These included vitamins, thiamine (vitamin B1), retinol (vitamin A) pyridoxine (vitamin B6), pyridoxal and pyridoxate) and cofactors, quinolinate, 1-methylnicotinamide and trigonelline, with therapeutic, antioxidant and anti-inflammatory properties. There was also fold-increases in rice bran-derived phenolics, namely 2-hydroxyhippuarte, 3-(3-hydroxyphenyl)propionate and 3-phenylpropionate at both 10 and 14 weeks when compared to control. The bioavailability of these bioactive phenolic compounds was further supported by colonic tissue metabolite profiling. Shifts in cellular energy metabolism, shown by citrate, aconitate, and malate; and in lipid metabolites namely (glycerol 3-phosphate, monoacylglycerols (1-oleoylglycerol (18:1) and 2-linoleoylglycerol (18:1)) and diacylglycerols (palmitoyl-linoleoyl-glycerol (16:0/18:2) and oleoyl-linoleoyl-glycerol (18:1/18:2) were detected as novel mechanisms for rice bran mediated-inhibition of colon cancer. TCA cycle metabolites may reflect the favorably altered intestinal microenvironment for depletion of cancer cells. This study supports a time series of fecal metabolic profiles associated with dietary rice bran alongside identification of novel mechanism(s) by which rice bran protects against or prevents progression of colon cancer. Citation Format: Petronella R. Hove, Annika Weber, Bridget Baxter, Hend Ibrahim, Kristopher Parker, Komal Raina, Elizabeth P. Ryan. Fecal metabolic changes following rice bran supplementation in the murine model for colitis associated cancer of the colon [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2343.