(publications)

The major focus of the Simpson Laboratory is inflammatory bowel disease (IBD) in people and animals. The cause of IBD is unknown, but it is suspected to develop as a result of complex interactions between the enteric environment, e.g. the intestinal bacteria, dietary factors, and genetic susceptibility in the host.

Key aims:

a.  Elucidating the role of the enteric microflora in IBD: We have 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 Adherent and Invasive E. coli.

Mucosa-associated E. coli are also related to the degree of intestinal inflammation and clinical severity of IBD in cats, and ongoing studies are directed at characterizing these bacteria. Subsequent studies directed at elucidating the virulence of these novel E.coli are in progress, and have spurred collaborations to study E.coli involved with bovine mastitis and metritis.

Boxer dog with severe weight loss due to Granulomatous Colitis	Endoscopic image of ulcerated colon mucosa in a Boxer dog with Granulomatous Colitis	FISH image showing multiple clumps of E. coli (orange) invading the colon mucosa

b.  Identifying host genetic factors related to IBD: The strong association of granulomatous colitis and Boxer dogs suggest Boxer dogs may have a heritable defect in their mucosal losing enteropathy (PLE) have an unusual histologic intestinal morphology, characterized by the presence of large numbers of crypt cysts. In ongoing studies we are seeking to identify the genetic basis of granulomatous colitis in Boxer dogs and PLE in Yorkshire terriers, using a combination of candidate gene and genome-wide analysis.

(publications)

Our work on Helicobacters has sought to define the most common Helicobacter species infecting dogs and cats. We have explored in depth the histologic and the serologic response to infection, in both naturally acquired and experimental infections. We have discovered that the types of Helicobacters most commonly found in dogs and cats include: H. felis, H. heilmannii, H. bizzozeronii, H. heilmannii, and H. salomonis.

In people, H. pylori is the dominant infecting Helicobacter species, with considerably greater pathogenicity and potential to cause gastritis, gastric ulceration, and gastric cancers. The lab has developed real-time PCR assays to quantify the cytokine response to Helicobacter infection, and have observed an inflammatory response dominated by the upregulation of IL1b, IL-8, IFN-g, similar to H. pylori infection in people.

We have also investigated 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, and cats, dogs and pigs are considered the most likely sources of infection. We have shown that the subtypes of “H. heilmannii “ present in dogs and cats are not the same as those usually found in people, suggesting that dogs and cats are actually a minor source of infection with “H. heilmannii”.

We have also demonstrated that Helicobacteriaceae in the oral cavity of dogs is predominantly of the species Wollinella succinogenes, rather than Helicobacter spp. Through collaboration with the Scanziani laboratory in Milan, we have found that the cecum and colon of healthy dogs are heavily colonized by enterohepatic Helicobacters. We have also found evidence to support the involvement of Helicobacter spp. in hepatic inflammation in some cats.

• The role of the mucosa-associated microflora in canine IBD
  Sponsored by the Morris Animal Foundation and Nestle-Purina.
• Granulomatous Colitis (or Histiocytic Ulcerative colitis) in Boxer dogs:

  Sponsored by the Cornell Center for Vertebrate Genomics.

• Protein Losing Enteropathy in Yorkshire terriers:

  Sponsored by the RCVS Trust, UK and the AKC.

• Intestinal microflora in cats with chronic enteropathies:

  Sponsored by the Feline Health Center at Cornell University.

• The role of the gastric microflora in gastric ulceration in horses.