TABLE OF CONTENTS

TITLE PAGE-       –         –         –         –         –         –         –         i

CERTIFICATION-          –         –         –         –         –         –         ii

DEDICATION-     –         –         –         –         –         –         –         iii

ACKNOWLEDGEMENT-        –         –         –         –         –         iv

TABLE OF CONTENTS-         –         –         –         –         –         v

CHAPTER ONE: INTRODUCTION

1.1     Background of the study- –         –         –         –         –         –         1

CHAPTER TWO

2.1     Composition and Structure of the Human

Gastro-intestinal Tract (GL) microbiota-       –         –         –         5

2.2     Development of the Human GL Microbiota- –         –         –         7

2.3     Factors Shaping the GL Microbiota-    –         –         –         –         10

2.4     Microbiota Diversity and Health-        –         –         –         –         17

2.5     Effects of Food and Drugs on the Gut Microbiota-  –         –         19

2.6     Manipulating the Gut Microbiota through Diet-      –         –         24

CHAPTER THREE: THE BIOCHEMICAL IMPORTANCE OF BACTERIA IN THE LARGE INTESTINE

3.1     The Medical Importance of the Human Microbiome-        –         29

3.2     The functional Role of the Gut Microbiome in

Health Disease and Drug Efficacy-      –         –         –         –         32

3.3     The Biochemical Importance of Bacterial in the

Large Intestine-      –         –         –         –         –         –         –         37

3.3.1  Epithelial Cell Interactions with Pathogens-  –         –         –         41

3.4     Mechanisms Utilized by Intestinal Pathogens

to Initiate and Induce Disease-   –         –         –         –         –         48

CHAPTER FOUR :SUMMARY AND CONCLUSION

4.1     Summary-    –         –         –         –         –         –         –         –         49

4.2     Conclusion- –         –         –         –         –         –         –         –         50

References

CHAPTER ONE: INTRODUCTION

1.1     Background of the Study

Humans evolved in the presence of numerous microbial communities that preceded the appearance of mammals on planet earth. The role of these microbial communities in our evolution is a matter of considerable interest. Indeed, comparative studies with germ free and conventional animals have established that the intestinal micro flora is essential for the development and function of the mucosal immune system during early life, a process that is now known to be important to overall immunity in adults. An absence of intestinal bacteria is associated with reductions in mucosal cell turnover, vascularity, muscle wall thickness, motility, baseline cytokine production, and digestive enzyme activity and with defective cell-mediated immunity (Macdonal and Monteleone 2005). Furthermore, the intestinal micro flora makes important metabolic contributions to vitamin K, foliate, and short-chain fatty acids, such as butyrate, a major energy source for enterocytes and also mediates the breakdown of dietary carcinogens. The bacterial flora of the gastrointestinal tract varies longitudinally, the oral cavity contains about zoo different species, the stomach is almost sterile and the bacterial content increases distally, with approximately 10⁸ bacteria per g (dry weight) of ideal contents and up to 10¹² bacteria per g (dry weight) of colonic contents (Berg, 1996). The conclusions of studies on the bacterial flora carried out some decades ago are still thought to be true. The large intestine contains organisms belonging to over 30 identified genera and as many as 500 separate species of phenotypes. The main types of bacteria are members of the genus Bacteroides, anaerobic gram-positive cocci, such as peplosureplococcus sp., Eubacterium sp., Lactobacillus sp., and Elostridium sp., More recent studies of large bowel biopsies confirmed that bacteroides was a dominant genus in the specimens examined (Swidsinski, et al., 2002).

Thus, intestinal bacteria represent a complex and incompletely understood micro-biome. Since certain organisms are thought to play a role in the onset of inflammatory disease of the bowel, whereas other organisms are considered protective micro-biome refers to the collective genomes of the microorganisms in a particular environment and micro-biota is the community of microorganisms themselves (box1), approximately 100 trillion micro- organisms (most of them bacteria, but also viruses, fungi and protozoa) exist in the human gastrointestinal tract (Backhed, 2005) the micro- biome is now best thought of as a virtual organ of the body. The human genome consists of about 23000 genes, whereas the micro- biome encodes over three million genes producing thousands of metabolites, which replace many of the functions of the host, (Moore et al., 2005) consequently influencing the hosts fitness phenotype and health. The micro biota offers many benefits to the host, through a range of physiological functions such as strengthening gut integrity or shaping the intestinal epithelium, harvesting energy (Den Besten et al., 2013), protecting against pathogens and regulating host immunity. However, there is potential for these mechanisms to be disrupted as a result of an altered microbial composition, known as dysbiosis. With increasingly sophisticated methods to profile and characterize complex ecosystems being developed a role for the micro-biota in a large number of intestinal and extra-intestinal diseases has become steadily apparent. This review summarizes our current understanding of the development and composition of the human GL micro-biota and its impact on gut integrity and host health.