Studying the roles of the microbial community structure as it relates to disease can give important insight into development of inflammation. This study employs concepts present in ecology to understand how altering bacterial communities in mammalian intestines affect inflammation at different stages of disease. The overall goal is to understand the role of the resident microbiota in initiation and progression of inflammatory bowel disease (IBD). Changes in the community can possibly act as a biomarker to diseases allowing preventative action to be taken or development of novel therapies.Work was done on two different models of IBD, dextran sodium sulfate (DSS)-induced murine colitis and Helicobacter hepaticus triggered inflammation in IL-10-/- mice (model of Crohn's disease). Through culture independent techniques, changes in the microbiota were investigated, together with alterations in host mediators. In the first model, whether DSS-induced colitis was associated with changes in the microbiota was investigated. DSS administration was associated with microbial changes in intestinal communities in mice and these changes were present at onset of inflammation and persisted through later stages of disease. In the second model, whether changes in microbial community structure affected disease severity was investigated. The H. hepaticus triggered disease model was used to explore this question, and it was found that H. hepaticus infection of mice with different microbial community structures resulted in similar disease outcomes. This indicated that disease severity was independent from antibiotic-induced changes in the microbial community in this model. We also show that the microbiota is essential in disease induction in mice in our colonies, as H. hepaticus monoassociated mice do not develop disease. These experiments demonstrate that the microbiota has important roles at several stages of disease, and these roles can be affected by other factors that influence IBD. In investigating stages at which the microbiota plays a role in IBD, we can better understand stages along disease progression when prognosis or treatment can be most effective.
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