Date of Award

2016

Document Type

Open Access Dissertation

Department

Exercise Science

Sub-Department

The Norman J. Arnold School of Public Health

First Advisor

Raja Fayad

Abstract

The microbiome forms an integral part of the gut microenvironment. Once ignored, the topic has gained momentum in research during the past decade, where studies have strongly suggested the association of microbiota with health and a misbalance thereof, to many disease conditions ranging from inflammation and colitis to diabetes, obesity and colon cancer. The Human Microbiome Project (HMP, NIH common fund - 2008) has used a variety of high throughput analyses in order to study gut microbiota in health. The consortium has so far been able to isolate and characterize more than 1,300 reference bacterial strains from the human body. The large amount of data generated has led to a baseline need to address the implications of different microbial members, or groups thereof, in health and disease. The microorganisms residing in the gut comprise of bacteria, archaea, fungi and viruses that are distributed throughout the length of the gastrointestinal tract. While there will be limitations to studying all types of microorganisms owing to their overwhelming numbers and types, our study is focused only on bacterial populations of the gut, and for the purpose of convenience, terms of gut microbiota/microbiome will be used for describing gut bacteria pertaining to the mice used in our study. The overall purpose of this study is to determine the effects of alterations in the gut microbiome on tumor development and inflammation, and if it leads to recolonization of the gut by altered bacterial communities. The working hypothesis was that an alteration of bacterial microbiome occurs during tumorigenesis and manipulation of the gut microbiome externally exacerbates the clinical symptoms associated with intestinal cancer, leading to higher gut and systemic inflammation. Specific aim 1 studied the composition of gut microbiota during the stages of tumor initiation and progression. It aimed at studying the gut microbial profiles pertaining to bacteria that reside inside the gut of the ApcMin/+ mice during normal conditions and comparing it to control mice. Among the different bacterial phyla residing in the murine gut, the Bacteroidetes and Firmicutes comprised of dominant bacterial populations. Specific aim 2 studied the effects of external manipulation of the gut microbiome on gut health and tumorigenesis. The manipulation of the gut microbial community was used to help elucidate how alterations in the gut microbiome effect the intestinal tumor and mucus production outcomes along with their effects on the gut health in measurable terms. Specific aim 3 studied the altered inflammatory response of the mouse gut with respect to relative abundances of the Bacteroidetes and Firmicutes bacterial phyla populations.

Rights

© 2016, Kamaljeet Kaur

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