The Effect of Fermentable Dietary Fibers on Colorectal Tumorigenesis

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- Author:
- Tian, Sangshan
- Graduate Program:
- Integrative and Biomedical Physiology
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- November 14, 2022
- Committee Members:
- Vishal Singh, Thesis Advisor/Co-Advisor
Connie Jo Rogers, Committee Member
Donna Korzick, Program Head/Chair - Keywords:
- Inflammatory bowel disease
colon cancer
dietary fiber
colitis
inflammatory bowel disease
colorectal cancer
dietary fibers - Abstract:
- Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Individuals with inflammatory bowel disease (IBD) are at high risk of developing CRC. The diminished CRC occurrence in patients with IBD who received optimal treatment to manage active intestinal inflammation signifies the importance of controlling ongoing intestinal inflammation to reduce the incidence and prevalence of IBD-related CRC. Dietary fibers (DFs) regulate many systems, including the gut microbiota and host intestinal immunity. DFs are metabolically inert to humans and mast be fermented by gut microbes. Both immune and metabolic functions of the lower gastrointestinal (GI) tract could be altered substantially in response to various amounts and types of DFs, specifically by the presence or absence of fermentable DFs (FDFs) such as inulin and partially hydrolyzed guar gum (PHGG). Intriguingly, isolated dietary fiber supplementation is not found beneficial in all IBD patients and laboratory animal models. We theorize that in contrast to DFs naturally present (as a mixture of both fermentable and non-fermentable types) in fruits, vegetables, and whole grains, isolated FDFs fuel the growth of a selective group of bacteria (e.g., expansion of γ-proteobacteria) based on their specificity toward gut microbes. Such selective utilization of isolated FDFs promotes dysbiosis and susceptibility to colonic inflammation that can increase the risk of colorectal tumorigenesis. This study aimed to elucidate the effect of isolated FDFs (inulin and PHGG), commonly present in a wide range of processed foods, on colonic inflammation and colorectal tumorigenesis. In this study, we found FDF supplementation (inulin and PHGG) did not alter intestinal inflammation markers in healthy mice. However, inulin and PHGG potentiated and prolonged colonic inflammation and delayed mucosal healing in mice with colitis induced by dextran sulfate sodium salt (DSS), suggesting that FDFs may fuel inflammation in the inflamed gut. Chronic intestinal inflammation, which fuels the continuous turnover of cells in the intestinal lining, considerably increases the risk of colorectal tumorigenesis by increasing the chance of missense mutations that may lead to cancer. In line, we observed extensive colon tumorigenesis in both inulin and PHGG-containing diet-fed mice. Altogether, our experimental findings suggest that the consumption of isolated FDFs may increase the risk of colon cancer in patients with IBD by potentiating intestinal inflammation. Therefore, incorporating highly refined FDFs in processed foods should be cautiously approached as it may increase susceptibility to intestinal inflammation and CRC.