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Abstract
Inflammatory bowel disease (IBD) has posed serious threats to the human health, which lead to chronic malabsorption of nutrients, abnormal pain and rectal bleeding. Both genetic predisposition and environmental factors contribute to the onset of IBD. Multiple studies suggested that dysbiosis in colon plays an important role in the development of colitis, and gut microbiota composition are different between patients with IBD and healthy individuals. Intake of whole foods, such as fruits and vegetables, may confer health benefits to the host. The beneficial effects of fruits and vegetables mainly attribute to their richness of polyphenols and microbiota-accessible carbohydrates (MACs). Components in fruits and vegetables modulate composition and associated functions of the gut microbiota, while gut microbiota can transform components in fruits and vegetables to produce metabolites that are bioactive and important for health. Accumulating evidence suggests that colonic inflammation may be prevented by increased consumption of certain fruits and vegetables such as berries. Cranberry and strawberry are abundant of polyphenols with various health benefits. Most studies focused on extractable polyphenols (EP), non-extractable polyphenols (NEP) were often neglected, although NEP may possess important biological functions. NEP is not significantly released from the food matrix during digestion in the stomach or small intestine, therefor they reach colon nearly intact. In the colon, the potential interaction between gut microbiota and NEP could also play an important role in colon health. NEP could be biotransformed by gut microbiota to produce bioactive metabolites that may contribute to the promotion of colon health as well. Therefore, it is important to investigate the interaction of gut microbiota and NEP in the colon in terms of production of bioactive metabolites. Meanwhile, composition and functions of gut microbiota can be altered by the presence of polyphenols in the colon, which in turn could affect colon health. The objective of this work was to characterize EP and NEP fractions from whole cranberry and strawberry and determine their potential in anti-inflammation and anti-colon cancer. EP and NEP from cranberry and strawberry showed anti-inflammatory effects in inhibiting LPS-induced production of nitric oxide in macrophages, which was accompanied by decreased expression of iNOS and increased expression of HO-1. EP and NEP from cranberry and strawberry showed anti-cancer capacities in HCT116 cells. Flow cytometry analysis demonstrated that NEP caused a cell cycle arrest and induced a significant cellular apoptosis in colon cancer cells. Furthermore, this study determined the protective effects of whole strawberry (WS) against dextran sulfate sodium (DSS)-induced colitis in mice. In colitic mice, dietary WS reduced the disease activity index (DAI), prevented the colon shortening and spleen enlargement, and alleviated the colonic tissue damages. The abundance of pro-inflammatory immune cells was reduced by dietary WS in the colonic mucosa, which was accompanied by the suppression of overproduction of pro-inflammatory cytokines. Western blotting and immunohistochemical analysis revealed that dietary WS decreased the expression of pro-inflammatory proteins in the colonic mucosa. Moreover, dietary WS partially reversed the alteration of gut microbiota in the colitic mice by increasing the abundance of potential beneficial bacteria, e.g. Bifidobacterium and Lactobacillus, and decreasing the abundance of potential harmful bacteria, e.g. Dorea and Bilophila. Dietary WS also restored the decreased production of short chain fatty acids (SCFAs) in the cecum of the colitic mice. The results revealed the anti-inflammatory effects and mechanisms of dietary WS in the colon, which is critical for the rational utilization of strawberry for the prevention of inflammation-driven diseases.
Type
dissertation
Date
2020-02
Publisher
Degree
Advisors
License
License
http://creativecommons.org/licenses/by/4.0/