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CC BY-ND V4.0, Open Access
Dissertation
HEALTH BENEFITS OF DIETARY BIOACTIVE COMPOUND ON INFLAMMATORY BOWEL DISEASE AND COLORECTAL CANCER
Washington State University
Doctor of Philosophy (PhD), Washington State University
01/2022
DOI:
https://doi.org/10.7273/000004378
Handle:
https://hdl.handle.net/2376/118906
Abstract
The industrial revolution is associated with a surge in the number of cases of inflammatory bowel disease (IBD) in western countries. In recent years, the incidence of IBD is continuously rising in newly industrialized countries. Additionally, the risk of colorectal cancer significantly increased in IBD patients. Diet plays an important role in IBD development, especially for diet with high amounts of processed food and unsaturated fat, but low amounts of vegetables. In this dissertation, the effects of bioactive compounds on inflammatory bowel diseases and colitis associated colorectal cancer were examined by a series of studies. In the first study, mice were subjected to azoxymethane (AOM)/dextran sulfate sodium (DSS) treatment for inducing colorectal cancer. Grape pomace (GP) supplementation decreased tumor number, tumor size and pathological scores. Inflammatory response was also suppressed by dietary GP associated with inhibition of epithelial cell proliferation. Dietary GP protected DNA hypermethylation in the promoter of cdx2, a master regulator in intestinal epithelial differentiation.
In the second study, dietary aKG alleviated mucosal damage and macrophage infiltration into colonic tissue induced by DSS, consistent with suppressed gut inflammation and Wnt signaling. Dietary aKG enhanced M1 to M2 macrophage polarization and improved intestinal barrier function. Additionally, aKG supplementation led to elevated colonic aKG levels while decreasing 2-hydroxyglutarate levels suggesting lower glycolytic metabolism.
In the third study, the protective effects of dietary glucoraphanin (GRP) on inflammation and oxidative stress were examined in an acute colitis mouse model induced by DSS. Dietary GRP prevented DSS-induced body weight loss and colon shortening, which was associated with decreased inflammatory cytokines. Dietary GRP activated AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α and nuclear factor erythroid 2-related factor 2 (NRF2) in the colonic tissues of DSS-treated mice. Furthermore, GRP supplementation prevented mice from oxidative damage of the colon.
In conclusion, this project used DSS and AOM/DSS animal models to demonstrate the beneficial effects of bioactive compounds on IBD and colorectal cancer prevention. Importantly, these studies identified possible molecular targets for the beneficial effects of different bioactive compounds.
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Details
- Title
- HEALTH BENEFITS OF DIETARY BIOACTIVE COMPOUND ON INFLAMMATORY BOWEL DISEASE AND COLORECTAL CANCER
- Creators
- Qiyu Tian
- Contributors
- Min Du (Advisor)Meijun Zhu (Committee Member)Jennifer Watts (Committee Member)Zhihua Jiang (Committee Member)Martin Maquivar (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Animal Sciences, Department of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 164
- Identifiers
- 99900883135201842
- Language
- English
- Resource Type
- Dissertation