| Crohn's disease is a chronic inflammatory disease of the intestine in humans, with unknown cause. Johne's disease is a chronic intestinal disease of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), and has some features similar to Crohn's disease. Although MAP has been purported to play an etiologic role in Crohn's disease, this causal link is still under debate. The overall aim of this project is to analyze MAP strains from different hosts and regions in North Dakota, in order to better understand the pathogenesis and epidemiology of MAP strains and the relationship between MAP and Crohn's disease. The specific aims of this research are to (1) investigate the epidemiological evidence for MAP as a cause of Crohn's disease, (2) conduct a comparative causality study to investigate whether MAP or other enteric pathogens cause Crohn's disease, (3) evaluate the occurrence of MAP infections in cattle in North Dakota, 1995--2005, (4) analyze MAP strains from symptomatic and asymptomatic cattle, (5) investigate the biochemical variations of rapid and slow growing MAP strains and (6) evaluate MAP strains from low shedders and high shedders. MAP isolates were analyzed by biochemical and epidemiological methods. In addition, extensive literature review was performed to (1) determine the epidemiologic causal link between MAP and Crohn's disease and (2) determine whether MAP or other enteric pathogens cause Crohn's disease. Epidemiologic evidence supported the causal role of MAP in Crohn's disease. It was also demonstrated that MAP is the most implicated organism in the etiology of Crohn's disease when compared to other infectious agents. Statistical analysis revealed significant association (p < 0.05) between symptom status, growth rate and shedder status of isolates. Overall, this study strengthens the theory of strain sharing and supports an association between MAP and Crohn's disease. In addition, the understanding of the biochemical variation among MAP isolates will help in the future design of diagnostics, therapeutics and vaccines for Johne's and Crohn's diseases. |
