The endogenous microbiota of gastrointestinal tract play an important role in maintenance of human health and development of disease. Some critical functions of the commensal flora for the host include regulation of fat storage, stimulation of intestinal angiogenesis, and regulation of epithelial homeostasis. Although intestinal microbial flora outnumber human cells by an order of magnitude, this complex community is not well characterized, and its diversity in health and disease is poorly defined. The main reasons for this shortcoming are inter-individual differences, sampling difficulties, insensitivity and limitations of methodology, and the fact that only about 30% of the microorganisms can be cultured. However, recent advances in molecular techniques have helped to characterize human gut flora in normal and diseased states. Inflammatory bowel disease (IBD) is a group of chronic disorders that cause inflammation in the intestines. This group of disorders comprise life impairing and relapsing illnesses that have no cure, affect close to 1.4 million Americans, and cost billions of dollars/year to health care systems. There is no known single cause for IBDs, and they are increasing in incidence, especially in Western countries. Multiple studies have implicated bacteria in the etiology and pathogenesis of IBDs. We have taken a Systems Biology approach to identify patterns of dysbiosis in IBDs. Our goals were: 1) to confirm the correlation between bacterial communities residing in the gastrointestinal tract and the occurrence of the disease in IBD patients, and 2) to determine if changes in the bacterial community (dysbiosis) cause the disease or if the dysbiosis occurs after the start of inflammatory process. Our main observations are that the mucosal biofilm is more correlated with disease etiology than stool. Our study also demonstrates that knowledge discovery approach could drive the development of new testable hypotheses that can be validated experimentally in the future.
|Advisor:||Gillevet, Patrick M.|
|Commitee:||Baranova, Ancha, Christensen, Alan H., Jonas, Robert B.|
|School:||George Mason University|
|School Location:||United States -- Virginia|
|Source:||DAI-B 75/04(E), Dissertation Abstracts International|
|Subjects:||Molecular biology, Ecology, Bioinformatics|
|Keywords:||Bacteria, Dysbiosis, Gut, Ibd, Inflammatory bowel disease, Microbiome|
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