(P13-041-23) Dietary Fibers Inulin and Partially Hydrolyzed Guar Gum Exacerbate Colitis and Colorectal Tumorigenesis

Objectives: Colorectal cancer is the second most common cause of cancer-related death in the United States. Patients with inflammatory bowel disease (IBD) are at higher risk of developing colon cancer. A processed diet with low dietary fibers (DFs) and subsequent gut microbiota dysbiosis contributes to the pathogenesis of IBD. Therefore, the fortification of refined DFs in the processed diet is viewed as a potential strategy to improve gut health. However, whether DFs improve or deteriorate IBD and colitis-associated colon cancer (CAC) is unclear. This study assessed the effect of two soluble DFs (SDFs), inulin, and partially hydrolyzed guar gum (PHGG), on colitis and CAC development.

Methods: Wild-type (4-week-old, either sex, n=5-7/group) mice received inulin, PHGG, or cellulose (control) containing diets for 4 weeks. Colitis was induced in a subset of mice by dextran sodium sulfate (DSS, 1.4%w/v-7 days). In another set of mice, CAC was instigated by three 7-day alternate cycles of DSS following an initial dose of azoxymethane (AOM; 7.5 mg/kg b. wt.; i.p.).

Results: Relative to the control diet (10% cellulose) group, the level of colonic inflammation markers (lipocalin2 and interleukin-1β) were elevated in both inulin (7.5% inulin and 2.5% cellulose) and PHGG (7.5% PHGG and 2.5% cellulose)-fed groups. The SDFs-fed group exhibited more severe weight loss, rectal bleeding, splenomegaly, and mucosal damage than controls. We next examined the effects of SDFs on CAC development. Surprisingly, significant mortality during the DSS cycle was observed in the inulin (~50%) and PHGG (~70%) groups. Consequently, the mice which completed the study exhibited extensive colon tumorigenesis compared with controls. Notably, only one out of fourteen mice on the control diet developed colon tumors. Immunohistochemical characterization of colon tumors showed higher expression of the proliferation marker Ki67 and activation of the Wnt signaling pathway, as evidenced by increased intracellular and nuclear localization of β-catenin in the SDFs-fed groups.

Conclusions: Our results suggest that SDFs promote colon tumorigenesis. Therefore, the incorporation of refined SDFs in processed foods should be cautiously approached as it may increase susceptibility to CAC.

Funding Sources: Career Development Award [ID# 597229] from the Crohn’s & Colitis Foundation (CCF) to VS