LAUSR

We previously reported that the grape pomace had a protective role against colorectal cancer development. This study is to assess the role of fecal metabolites in mediating the observed beneficial effects of grape pomace. Nine-week-old female mice were fed a control diet (CON) or CON with 5% grape pomace for 2 weeks when mice were subjected to azoxymethane (AOM)/dextran sulfate sodium (DSS) for colorectal cancer (CRC) induction. Fecal samples collected at the end of dietary treatment were used to profile the fecal metabolomic changes in response to grape pomace supplementation using gas chromatography-mass spectrometry (GC-MS) based metabolomic analysis. Dietary grape pomace supplementation resulted in significant changes of a total of 29 compounds, which included bile acids, amino acids, fatty acids, phenols/flavonoids, glycerolipids, carbohydrates, organic acids, and others. These differential compounds were enriched in several pathways including alpha-linolenic acid and linoleic acid metabolism, phenylacetate metabolism, malate-aspartate shuttle, tyrosine metabolism, taurine, and hypotaurine metabolism, and others. The major changes of metabolites in feces include increased deoxycholic acid and decreased L-Aspartic acid, L-Proline, and Valine amino acid contents, all of which have strong associations with intestine inflammation and carcinogenesis. Urease hydrolyzes urea to produce ammonia, which increases amino acid concentrations in the gut lumen. Consistently, the urease activity of fecal samples was significantly reduced in the grape pomace supplemented group compared to the control group. The increase of fecal deoxycholic acid and the reduction of urease and amino acids might be key factors contributing to the beneficial effects of grape pomace supplementation against CRC development. USDA-NIFA and WSU ERI competitive grant.