Reduction in Mucosal Barrier Markers with Soy Protein Diet but not Lactobacillus rhamnosus GG in DSS-Treated Mice

Abstract

vii CHAPTER 1: LITERATURE REVIEW Physiological and cellular characterization of the colon mucosa 1 Overview of inflammatory bowel diseases 5 Etiology of IBD 6 IBD animal models: classification, DSS model 10 MUC genes and DSS induced colitis 13 TFF genes and DSS induced colitis 14 TNF-α as an inflammatory marker in DSS induced colitis 16 Probiotic and barrier function 18 Dairy proteins and barrier function 20 Soy protein and barrier function 22 Hypothesis 25 iii CHAPTER 2: REDUCTION IN MUCOSAL BARRIER MARKERS WITH SOY PROTEIN DIET BUT NOT LACTOBACILLUS RHAMNOSUS GG IN DSS-TREATED MICE Abstract 26 vi ACKNOWLEDGEMENTS I would like to take this opportunity to express my acknowledgements to those who helped me during the two years I conducted research and wrote this thesis. I thank Dr. Ruth S. MacDonald for her guidance, support and patience throughout my education. Her encouragement always inspired me when I came across difficulties in my research and in the writing of this thesis. I admire her dedication, passion and confidence as a scientist and her responsibility as an educator. I thank Dr. Joseph Przybyszewski for his constant help and support. He taught me a lot of experimental skills and assisted me to complete the study and analyze the data. This work could not be possible without his support. I also thank my committee members for their contributions to my education: Dr. Stephanie Clark, Dr. Suzanne Hendrich, Dr. Michael Wannemuehler and Dr. Eric Weaver. They gave me countless valuable suggestions about my research and made this work better. I would also like to thank Dr. Byron Brehm-Stecher for providing the facility to culture the probiotic and examine the histological sections, Jack Gallup for helping with the PCR, Debjani Mitra for preparing the probiotic, and Chad Becker for his assistance in this project. Last but not least, I would like to express my appreciation to my family and friends for their love and support. vii ABSTRACT Inflammatory bowel disease (IBD) is a common ailment affecting people of all ages. Even though the pathogenesis of IBD has not been fully elucidated, there is evidence that it involves interactions between genetic susceptibility, aberrant activation of the immune system, and the environment. Inflammation of the colon (colitis) results in pain, diarrhea, hemorrhage, and weight loss. Within the colon, the family of mucins (MUC) and trefoil factors (TFF) facilitate mucosal protection. Recent studies found that probiotic administration could influence the colonic mucin layer. Additionally, food components may affect gut microflora or have influence on the mucin barrier. Our aims were to explore the role of probiotic administration in modulating MUC and TFF gene expression in the dextran sodium sulfate (DSS) induced colitis mouse model, and to examine interactions with casein, whey, or soy protein diets. C57BL/6 mice were assigned to three diet groups. Diets were formulated to substitute casein, whey or soy protein on an equivalent basis. On day 6, each diet group was divided into 2 g...