INFLAMMATORY BOWEL DISEASE Edited by Imre Szabo INFLAMMATORY BOWEL DISEASE Edited by Imre Szabo Inflammatory Bowel Disease http://dx.doi.org/10.5772/46222 Edited by Imre Szabo Contributors Hyunjo Kim, Rahul Anil Sheth, Michael Gee, Valeriu Surlin, Adrian Saftoiu, Catalin Copaescu, Diehl, Yves-Jacques Schneider, Alina Martirosyan, Madeleine Polet, Alexandra Bazes, Thérèse Sergent, Ladislava Bartosova, Michal Kolorz, Milan Bartos, Katerina Wroblova, Michael Wannemuehler, Albert E. Jergens, Amanda E. Ramer-Tait, Anne-Marie C. Overstreet, Brankica Mijandrusic Sincic, Ana Brajdić Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. 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Publishing Process Manager Danijela Duric Technical Editor InTech DTP team Cover InTech Design team First published December, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from [email protected] Inflammatory Bowel Disease, Edited by Imre Szabo p. cm. ISBN 978-953-51-0879-5 Contents Preface VII Section 1 Pathogenesis of Inflammatory Bowel Disease 1 Chapter 1 Insights to the Ethiopathogenesis of the Inflammatory Bowel Disease 3 Ana Brajdić and Brankica Mijandrušić-Sinčić Chapter 2 Gene Polymorphisms and Inflammatory Bowel Diseases 3 Bartosova Ladislava, Kolorz Michal, Wroblova Katerina and Bartos Milan Chapter 3 The Role of the Microbiota in Gastrointestinal Health and Disease 23 Anne-Marie C. Overstreet, Amanda E. Ramer-Tait, Albert E. Jergens and Michael J. Wannemuehler Chapter 4 Fibrosis in Crohn’s Disease 73 Lauri Diehl Section 2 Management of Disease 175 Chapter 5 The Imaging of Inflammatory Bowel Disease: Current Concepts and Future Directions 151 Rahul A. Sheth and Michael S. Gee Chapter 6 An Update to Surgical Management of Inflammatory Bowel Diseases 177 V. Surlin, C. Copaescu and A. Saftoiu VI Contents Section 3 Future Therapeutic Directions in IDB 225 Chapter 7 Targeting Colon Drug Delivery by Natural Products 197 Hyunjo Kim Chapter 8 Food Nanoparticles and Intestinal Inflammation: A Real Risk? 227 Alina Martirosyan, Madeleine Polet, Alexandra Bazes, Thérèse Sergent and Yves-Jacques Schneider Preface Inflammatory bowel disease (IBD) is a term for a two very different and yet in many characteristics congruent chronic inflammatory disorder of the intestinal tract. Crohn’s disease (CD) and ulcerative colitis are two principal components of IBD. Both CD and ulcerative colitis are considered as multifactoral diseases. For long period of time we keep these inflammatory intestinal disorders as the result of environmental factors and immunological disturbances manifested in persons with genetic predisposition. The pathogenesis of IBD has remained largely unknown, but surely involves environmental factors, immunological factors in a complex form. Increasing disease prevalence and gathered lot of new research data on IBD suggested the pretence for review. Epidemiological studies have shown that prevalence of IDB has dramatically increases in western world probably due to western lifestyle. Environmental factors are suggested to have major role in development of diseases connected to westernalization of the lifestyle. These factors include smoking, use of antibiotics and non-steroidal anti-inflammatory drugs, stress, various infections and diet. The initiating mechanisms of their actions are still not understood. Research has revealed several genetic factors contributing to IDB pathogenesis; more than a hundred IDB genes, loci and their allele variation have been defined (e.g. NOD2/CARD15, IL23, ATG16L1, IRGM, ICAM-1, CCR5, TLR4, TNFα). Intestinal stricture is a serious and late complication of CD. Recent studies have identified certain disease specific characteristics that may be used in identifying individuals having higher risk for stricture development. These are lower age at initial diagnosis of CD, need for steroid therapy at the diagnosis, perianal fistulizing disease or small intestinal localized disease. Anti-Saccharomyces cerevisiae antibody (ASCA) levels were also found to be correlated to fibrostenosing or penetrating disease behaviour. Recently, other serological markers (anti-I2 and anti-CBir1), fibronectin, bFGF and YKL-40 glycoprotein of the chitinase family have been shown to lead to the hyperplasia of the intestinal muscle layers and deposition of collagen. Determination of gene polymorphism can also be important in regarding the prediction of therapy response. Since no curative therapy for IBD exists, pharmacological therapy mainly focuses on inflammation control. IBD pharmacotherapy utilizes a wide scale of drugs for inflammation reduction including aminosalicylates, glicocorticoids, immunomodulators and biological therapy. Their pharmocodinamics and pharmacokinetics can be altered by polymorphisms of certain gene coding proteins resulting faster drug elimination, tolerance or more side affect development. Namely, the form of N-acetyltransferase in slow acetylators can develop more side effects for sulfasalazine, mutation of glucocorticoid receptor-β lead to decreased affinity to exogenous glucocorticoids, mutations of thiopurine VIII Preface S-methyltransferase defining allelic variations determine the likeliness of leucopenia and thrombocytopenia development during azathioprine or 6-mercaptopurine treatment. Patients who are homozygous for certain standard alleles of NOD2, TLR4 and TNFα are more often resistant to infliximab therapy. The role of altered composition in intestinal microbiota has also been emphasized in the development of IBD over the years. The gut microbiota composition varies upon individual but remains highly stable containing large amount of Bacteroidetes, Firmicutes, Acinetobacter, Proteobacteria and Fusobacteria containing 150 times larger genetic information than the human genome. This changed composition in IBD surely affects normal barrier function, cell metabolism, antibiotic function and inflammatory responses. This book is trying to give further research data to answer the main question whether altered microbiota composition is a cause of or a consequence of the inflammatory state. In the first part of this book you can read chapters for outstanding researchers on the ethiopathogenesis of IBD including a reviews on environmental factors, genetic predisposition (including gene polymorphisms influencing disease development, efficacy of therapy with standard aminosalicylates, glucocorticoids and immunomodulators as well as biological therapy), altered immune response effecting various components of the innate and acquired immune system leading to loss of tolerance to commersal enteral bacteria and to gut dysbiosis. In the second part of the book clinicians show the management of IBD including the presentation of use of modern radiological diagnostic modalities in the diagnosis and identification of extent and activity of IBD. The place of surgical therapy in the management of IBD patients will be discussed by showing up-to-date minimally invasive techniques along with the long-term results of classical surgical options. The last part of the book focuses on future directions of IBD therapy utilizing new pharmacological methods for more effective drug delivery. Potential role of liposomes and nanoparticules (NP) will be highlighted in the treatment of IBD and colon cancer. Data will show that certain nanopaticules, like Ag-NPs or chitosan, may enhance the epithelial permeability and could therefore serve as an effective carrier for drug delivery, but also might favour the systemic absorption of toxins or other NPs that would likely cause immune activation. You can find more interesting data on the beneficial role and night-side of colon targeting drug delivery systems in this last part of the book. I am sure together with the Commissioning Editors and the Publisher that all readers, researcher, clinicians and novice readers, will receive lot of new scientific information by reading this book. I wish to thank the outstanding work of all authors, the invitation to the publisher and the excellent support throughout the publishing process to the commissioning editors, Ms. Ivona Lovric, Ms. Danijela Duric and Mr. Vedran Greblo. Imre Szabo MD, PhD Division of Gastroenterology First Department of Medicine University of Pécs Hungary Section 1 Pathogenesis of Inflammatory Bowel Disease Chapter 1 Insights to the Ethiopathogenesis of the Inflammatory Bowel Disease Ana Brajdić and Brankica Mijandrušić-Sinčić