Scientific Abstract

Proposal No. IBD-0183
Principal Investigator:  Hazel M. Mitchell, Ph.D.
Applicant Organization:  The University of New South Wales (Australia)
Project Title:   Investigation of the role of members of the Helicobacteriaceae in Crohn’s disease
Period of Award:  September 7, 2006 – March 6, 2008

Recent studies in animal models of IBD have focused attention on a group of bacteria that naturally colonize the mucus layer covering the intestinal epithelium of a large range of mammalian hosts, the entero-hepatic Helicobacter species. Given that these organisms reside in the mucus layer close to the intestinal epithelium and can induce IBD-like inflammation in animal models, we hypothesized that these bacteria were prime candidates to initiate and/or maintain the inflammation associated with CD.

To test this hypothesis, we conducted a pilot study in children presenting for colonoscopy and a group of control asymptomatic children to determine the presence and location of these bacteria in the colon. Viable members of the Helicobacteriaceae are present in the mucus layer covering the colon of children with CD but not in controls. Based on these findings and the strong association between these organisms and IBD in immuno-deficient animals, we hypothesize that Helicobacteriaceae play an important role in the initiation and/or maintenance of CD.

The aim of the proposed studies is to determine, using both molecular and cultural techniques, the role of the Helicobacteriaceae family in the etiology of CD in children. These studies are unique and are of particular significance as they are conducted in children, who are free of significant confounding factors, and who reside in three geographic locations. The specific goals are to:
 

• Collect intestinal biopsies and fecal samples from children undergoing colonoscopy and diagnosed with CD at hospitals in three geographic locations, Australia, Canada and USA.
• Collect fecal samples from asymptomatic children (age & ethnicity matched to CD children) attending each of the above locations for conditions other than gastrointestinal conditions.
• Detect using molecular techniques, members of the Helicobacteriaceae in colonic biopsies and/or feces from these children and where present identity the species involved.
• In those CD children shown to be positive for members of the Helicobacteriaceae, to culture and where successful, identify and characterize the species involved.
• Assess, in children with CD, the location (if present) of these bacteria using FISH.
• Determine if an association exists between members of the Helicobacteriaceae family and CD.

If members of the Helicobacteriaceae are shown to be associated with CD, significant benefits to patients can be predicted. Firstly, diagnostic tests could be developed to rapidly identify these bacteria, thus allowing rapid diagnosis. Secondly, and of particular significance to those with CD, these bacteria could be eradicated using antibiotics. Thirdly, successful culture of these bacteria, will allow studies to be conducted that can ascertain the pathogenic mechanisms of these bacteria.