Internal Medicine and Gastroenterology
The Simpson laboratory is focused principally on host bacterial interactions in the gastrointestinal tract. Specifically we are interested in the role of Helicobacter in gastrointestinal and hepatic infllammation, and the impact of the intestinal microflora (particularly a novel group of adherent and invasive E. coli) on inflammatory bowel disease.
Role of Helicobacter in gastrointestinal disease:
These studies have centered on naturally acquired and experimental Helicobacter infections of dogs and cats. Initial studies sought to define the Helicobacter species infecting dogs and cats in the USA and other countries (H. felis, H. heilmannii, H. bizzozeronii, H. heilmannii, H. salomonis), and evaluated the histologic and serologic response to infection. Experimental infections of cats and dogs with H. felis, and cats with H. pylori, were performed to determine their effect on gastric function and pathology. Chronic infections were not associated with the hypergastrinemia and acid-secretory changes observed in H. pylori infected people.
The lab has developed species-specific real-time PCR assays to quantitate the cytokine response to infection, and have observed an inflammatory response dominated by the upregulation of IL1b, IL-8, IFN-g, similar to H. pylori infection in people. The lab has also focused on the pathogenesis and virulence of H. pylori infection in cats, aiming to characterize putative bacterial determinants of virulence in-vivo. Infection with H. heilmannii is considered a potential zoonosis, with cats, dogs and pigs considered the sources of infection. The laboratory has shown that the subtypes of "H. heilmannii " present in dogs and cats are not the predominant ones in people, providing evidence that dogs and cats are likely a minor source of infection with H. heilmannii. We have since demonstrated that Helicobacter DNA is detectable in the oral cavity of dogs raising the possibility of oral transmission to dogs and people. In a recent study we found evidence to support the involvement of Helicobacter in infllammatory liver disease in cats.
Inflammatory Bowel Disease:
The other major focus of the laboratory is inflammatory bowel disease. Little is known about the etiopathogenesis of inflammatory bowel disease in dogs and cats and people Using the quantitative cytokine methodologies developed to study Helicobacter infection the lab has prospectively characterized the immune environment in the small intestine of cats with lymphoplasmacytic enteritis and gastrointestinal lymphoma. We have also investigated the relationship of mucosal bacteria to IBD in dogs, cats and people using contemporary culture independent techniques. This has lead to the discovery that granulomatous colitis in Boxer dogs is associated with an invasive E.coli infection, and that the ileum of people with Crohn's disease is selectively enriched in a similar group of E.coli. Interestingly, mucosal E.coli are also related to the degree of intestinal inflammation and clinical severity of IBD in cats. Subsequent studies directed at elucidating the virulence of these novel E.coli are in progress,and we have active collaborations to study E.coli involved with bovine mastitis and metritis.