Scientific Abstract

Proposal No. IBD-0207R
Principal Investigator:  Saleh A. Naser, Ph.D.
Applicant Organization:  University of Central Florida (Orlando, U.S.A.)
Project Title:  Role of Mycobacterium paratuberculosis (MAP) in family members with Crohn’s disease: genetic link and environmental influence
Period of Award:  January 1, 2008 – February 28, 2011

The cause of Crohn’s disease (CD) has yet to be determined. One theory is that organisms such as Mycobacterium paratuberculosis (MAP) may be associated with CD pathogenesis. Implication or exclusion of MAP bacterium will provide significant impact on IBD with regard to diagnosis, treatment and epidemiology. Because it has been determined that MAP can be excreted in the milk of infected cattle, can cross the species barrier between cattle and humans, and may be present in dietary products and meat, investigating the role of MAP in CD etiology and its possible zoonotic potential is imperative. Although detection of MAP DNA will not reflect on any role for MAP in CD etiology, it may aid in the assessment of MAP spread in the environment. Development of real time RT-PCR could be used to probe CD patients associated with viable MAP replacing a long-term culture technique.

Culture of MAP from peripheral blood and breast milk from Crohn’s patients in our laboratory is an intriguing observation and should be built on. Other laboratories, including Collins Laboratory at UWS and CDC, have recently cultured MAP from the blood of IBD patients. Genetic susceptibility studies in CD suggested that an average of 25% of CD patients have mutations in the NOD2 resulting in susceptibility to intracellular infections in these hosts. Despite all these findings, none of these studies have investigated any correlation between the presence of MAP (an intracellular pathogen) in tissue and blood and in association with NOD2 mutation in IBD patients. Other intriguing questions need to be addressed including any possible correlation between MAP infection, NOD2 mutation and the use of immunosuppressant in IBD. This is the first comprehensive study designed to investigate any correlation between intestinal colonization of MAP and bacteremic MAP infection (systemic) in association with the frequency of NOD2 gene mutation and current use of immunosuppressant. If proven, the impact will be significant regarding the way CD is diagnosed and treated.

Consequently, this study is designed to go beyond reporting the presence or absence of MAP in CD patients. All patients including family members with CD involved in this study will be investigated for the presence and sharing of MAP strains in correlation with genetic susceptibility, current use of immunosuppressant, and the epidemiology and familial aggregation of CD. Ultimately, this study may provide new information regarding the safety of our food chain and the development of precautionary protocols for family members with Crohn’s associated with MAP. Regardless whether MAP presence in CD patients is causative or casual, the bacterium should be eradicated in these patients. It is imperative that this important and well-needed and designed study will have significant impact on CD diagnosis, treatment and familial aggregation.