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Promotion of Colon Health by Strawberry and Cranberry

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Promotion of Colon Health by Strawberry and Cranberry University of Massachusetts Amherst ScholarWorks@UMass Amherst Doctoral Dissertations Dissertations and Theses March 2020 PROMOTION OF COLON HEALTH BY STRAWBERRY AND CRANBERRY Yanhui Han University of Massachusetts Amherst Follow this and additional works at: https://scholarworks.umass.edu/dissertations_2 Part of the Food Biotechnology Commons, Food Chemistry Commons, and the Food Microbiology Commons Recommended Citation Han, Yanhui, "PROMOTION OF COLON HEALTH BY STRAWBERRY AND CRANBERRY" (2020). Doctoral Dissertations. 1828. https://doi.org/10.7275/bcy8-p973 https://scholarworks.umass.edu/dissertations_2/1828 This Open Access Dissertation is brought to you for free and open access by the Dissertations and Theses at ScholarWorks@UMass Amherst. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of ScholarWorks@UMass Amherst. For more information, please contact [email protected]. PROMOTION OF COLON HEALTH BY STRAWBERRY AND CRANBERRY A Dissertation Presented by YANHUI HAN Submitted to the Graduate School of the University of Massachusetts Amherst in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY February 2020 The Department of Food Science © Copyright by Yanhui Han 2020 All Rights Reserved PROMOTION OF COLON HEALTH BY STRAWBERRY AND CRANBERRY A Dissertation Presented by YANHUI HAN Approved as to style and content by: _______________________________________ Hang Xiao, Chair _______________________________________ Guodong Zhang, Member _______________________________________ Zhenhua Liu, Member ____________________________________ Eric A. Decker, Department Head Department of Food Science DEDICATION I dedicate this thesis to my beloved families and friends ACKNOWLEDGEMENTS I would like to express my sincere gratitude to my advisor, Dr. Hang Xiao, for providing me an opportunity to fulfill my dream in his group. With his continuous support, his kind guidance, his motivation and insight on science, I was trained and prepared to be a mature researcher. Without his help and guidance, I cannot complete this work. Also, I would like to thank my committee members, Dr. Guodong Zhang and Dr. Zhenhua Liu, for their kindly guidance, valuable time, feedbacks and recommendations that improve the quality of this dissertation. Many thanks to all my lab members, past and present: Mingyue, Zili, Nok, Zhengze, Fang, Xiaokun, Xiaoqiong, Min, Che, Jiazhi, Meigui, Lingfei, Daoyuan, Qi, Hengjun, Tim and Will, for the past four years. Thank Chiayu for lab general maintaining and help. I would like to thank all of Food Science faculties, staffs and students, especially Mary, Fran, Deby, Stacy and Dave, for their help. Last but not least, I would like to express my gratitude to my family for their love and support. v ABSTRACT PROMOTION OF COLON HEALTH BY STRAWBERRY AND CRANBERRY FEBRUARY 2020 YANHUI HAN B.S., SOUTHWEST UNIVERSITY, CHINA Ph.D., UNIVERSITY OF MASSACHUSETTS, AMHERST, MA, USA Directed by: Professor Hang Xiao 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 vi 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 vii 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. viii TABLE OF CONTENTS Page ACKNOWLEDGEMENTS ................................................................................................ v ABSTRACT ....................................................................................................................... vi LIST OF TABLES ............................................................................................................ xii LIST OF FIGURES ......................................................................................................... xiii CHAPTER 1. INTRODUCTION .......................................................................................................... 1 2. LITERATURE REVIEW ................................................................................................ 5 2.1 Interactions between Whole Foods and Gut Microbiota in healthy Populations ...... 7 2.1.1 Whole Fruits and Vegetables Beneficially Impact Gut Microbiota ................. 13 2.1.2 Interaction between Microbiota-Accessible Carbohydrates (MACs) and Gut Microbiota ................................................................................................................. 16 2.1.3 Interactions between Polyphenols and Gut Microbiota ................................... 19 2.2. Whole Foods vs. Isolated Major Components of Whole Foods in Modulating Gut Microbiota ..................................................................................................................... 25 2.3. Whole Foods and Gut Microbiota-associated Diseases ......................................... 25 2.3.1 Obesity ............................................................................................................. 25 2.3.2 Colonic Inflammation ...................................................................................... 33 3. NON-EXTRACTABLE POLYPHENOLS FROM CRANBERRY: A POTENTIAL ANTI-INFLAMMATION AND ANTI-COLON CANCER AGENT .............................. 37 3.1 Introduction ............................................................................................................. 37 3.2 Materials and methods ............................................................................................ 39 3.2.1 Materials .......................................................................................................... 39 3.2.2 Extraction of EP ............................................................................................... 39 3.2.3 Extraction of NEP ............................................................................................ 40 3.2.4 Determination of total phenolic
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