Abstract 3461: Psyllium protects against high fructose diet induced exacerbation of colitis and colitis associated colorectal carcinogenesis

Abstract

Abstract Patients with longstanding Inflammatory Bowel Disease, including ulcerative colitis and Crohn's disease, are at an increased risk of developing colorectal cancer (CRC). Over the past three decades, there has been a significant increase in the consumption of fructose, a monosaccharide that has been linked to increased growth of experimental intestinal tumors. Additionally, recent evidence shows that feeding a diet high in fructose worsens acute experimental colitis. The aims of the current study were to 1) determine if a high fructose diet (HFrD) exacerbated chronic colitis in mice and led to enhanced colorectal tumorigenesis and 2) evaluate the potential chemopreventive properties of dietary fiber in this context. To carry this out, the azoxymethane (AOM)/DSS model of colitis-associated colorectal neoplasia was utilized in male C57BL/6J mice. In comparison to control AIN93G diet, an isocaloric diet supplemented with fructose led to worse chronic colitis including weight suppression, worse diarrhea, colon shortening and a higher histologic score. Tumor incidence, number and size were all increased (Ps<0.001) in the HFrD compared to control diet group. Because eliminating fructose from the diet is impractical, it is important to identify other potential dietary constituents that may minimize its harmful effects. Dietary fiber has been suggested to be beneficial for reducing the severity of colitis. Therefore, we next determined whether the severity of HFrD-associated acute colitis was altered by dietary psyllium, pectin, inulin or cellulose fibers. In comparison to the other three fibers, psyllium protected against acute DSS- induced colitis. It also led to a significant shift in the fecal microbiota. Finally, we tested whether psyllium would attenuate the worsening of chronic colitis and colitis-associated colorectal neoplasia mediated by HFrD. Using the AOM/DSS model, we found that psyllium fiber protected against the exacerbation of chronic colitis mediated by HFrD with improved diarrhea, bleeding and histologic score. Consistent with its ability to suppress HFrD-mediated exacerbation of chronic colitis, psyllium markedly suppressed the increase in colorectal tumor incidence, number and size in mice that received the HFrD. Taken together, these results indicate that feeding a HFrD exacerbated chronic colitis leading to increased colitis-associated colorectal tumorigenesis. Supplemental psyllium fiber attenuated these procarcinogenic effects of a HFrD. Citation Format: Srijani Basu, Ryohei Nishiguchi, David C. Montrose, Hannah Staab, Xi Kathy Zhou, Hanhan Wang, Melanie Johncilla, Rhonda K. Yantiss, Andrew Dannenberg. Psyllium protects against high fructose diet induced exacerbation of colitis and colitis associated colorectal carcinogenesis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3461.