Preface

**Section 3 Future Therapeutic Directions in IDB 225**

Hyunjo Kim

**VI** Contents

**Real Risk? 259**

Chapter 7 **Targeting Colon Drug Delivery by Natural Products 227**

Alina Martirosyan, Madeleine Polet, Alexandra Bazes, Thérèse

Chapter 8 **Food Nanoparticles and Intestinal Inflammation: A**

Sergent and Yves-Jacques Schneider

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 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**

**Pathogenesis of Inflammatory Bowel Disease**

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

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

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

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

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

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

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.

> **Imre Szabo MD, PhD** Division of Gastroenterology First Department of Medicine

> > University of Pécs

Hungary

more often resistant to infliximab therapy.

to gut dysbiosis.

VIII Preface

reading this book.

is a cause of or a consequence of the inflammatory state.

along with the long-term results of classical surgical options.

of colon targeting drug delivery systems in this last part of the book.

Ivona Lovric, Ms. Danijela Duric and Mr. Vedran Greblo.

**Chapter 1**

**Insights to the Ethiopathogenesis of the Inflammatory**

Inflammatory bowel disease (IBD) is a term that refers to two very different yet in many ways related phenotypes, Crohn's disease (CD) and ulcerative colitis (UC). It is well known that both of the two primary human inflammatory bowel diseases are characterized by

CD and UC are considered to be multifactorial diseases and the underlying pathological process seems to be a combination of genetic predisposition and immunologic disturbances. Being the largest surface in the human body and since it is constantly colonized by a highly diverse community of microbes that are in normal circumstances either commensal or bene‐ ficial to human health, the role of the intestinal microbiota in development of IBD has been thoroughly investigated over the years. It is now generally accepted that the commensal flora plays a central role in triggering and perpetuating the disease process. [1] Even though there are several logical arguments contributing to the theory that the intestinal microbiota plays a major role in the IBD development, the types of microbes involved have not been adequately described. Studies of experimental animal models of IBD uncover that the pres‐ ence of gut bacteria is essential in inflammation initiation and there is no disease onset in germ-free mice [2]. Furthermore, decreasing bacterial numbers in the intestine by using anti‐ biotics, can lead to clinical improvement and decreased inflammation in both humans [3]

Pathogenesis of the IBD is characterized by various genetic abnormalities that lead to overly aggressive altered immune response, triggered by heterogeneous environmental factors un‐ der the influence of the commensal intestinal microbiota. There is no single abnormality of the gastro intestinal tract that would lead to development of CD or UC. Only in correlation of those four mentioned main factors a dysbalance of the gastrointestinal tract develops,

and reproduction in any medium, provided the original work is properly cited.

© 2012 Brajdić and Mijandrušić-Sinčić; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is

© 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

chronic inflammation of the intestinal tract, yet their etiology still remains unclear.

**Bowel Disease**

http://dx.doi.org/10.5772/52970

and animal models of IBD [4, 5].

properly cited.

**1. Introduction**

Ana Brajdić and Brankica Mijandrušić-Sinčić

Additional information is available at the end of the chapter
