A Multidisciplinary Approach
We utilize a multidisciplinary approach and efforts to resolve pressing questions in four poorly understood gastrointestinal (GI) diseases (inflammatory bowel disease (IBD), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and peptic diseases - including peptic ulcer disease and non-ulcer dyspepsia), which are all linked through infectious agents as a causative factor.
These diseases are multidimensional and complex in nature, being caused by a number of interrelated microbial and/or other environmental factors in genetically predisposed individuals. Solving the etiologic, therapeutic and management issues of these gastrointestinal diseases is proving intractable from the perspective of small research teams working in isolation.
Our multidisciplinary research will catalog the phenotypic and genotypic expressions of the diseases, link these epidemiologically to potential and known causal factors, deconstruct the molecular genomics of the causal factors and then reassemble the information in order to better understand the diseases from a scientific and medical perspective. This, in turn, will lead to translational development of molecular diagnostic and therapeutic approaches. Subsequent research will then examine
The Inter-relationship of Diseases
The common link between the diseases under investigation is that they all show strong correlation with the presence of microbes and microbe-associated inflammation. This is a significant shift from what the medical community traditionally attributed to the cause of these diseases. The medical breakthrough illustrating that H. pylori was directly responsible for the onset of peptic ulcers has opened the door for other investigators to explore the role of microbes and gastrointestinal diseases.
This research includes (1) defining the role of H. pylori resistance to antibiotics and the host/pathogen relationship in mediating peptic ulcer disease; (2) demonstrating the role of intestinal bacterial flora in promoting IBD in genetically susceptible IL-10 knock-out mice, cataloguing the detrimental effects of specific species and the protective effect of probiotics; and (3) identifying retroviral etiologies for hepatobiliary diseases PBC and PSC, establishing an in vitro model to demonstrate Koch's postulates for PBC and demonstrating the utility of antiviral therapy for PBC.
Studying these "linked" GI disorders together provides synergism by permitting researchers to benefit from exposure to mechanistic and therapeutic advances in one section of research that could be relevant to one or all other sections. For example, environmental factors, genetic polymorphisms and novel therapies applicable to IBD may equally impact on the hepatobiliary disorders, which are often associated with the development of IBD. The pioneering effort in our research will realize the linkage between genes, microbes, GI disease and cancer. The search for genetic influences of the disease and gastrointestinal microbial colonization and interaction is highly innovative.
This multidisciplinary approach will not only identify new, but also explore established, links between the diseases, providing more comprehensive, holistic view of the diseases that will aid in their treatment and prevention, which will lead to improving the quality of life of patients.