Inflammatory Bowel Disease in Children
Inflammatory Bowel Diseases (IBD) that encompass ulcerative colitis (UC) and Crohn's disease (CD) are chronic relapsing idiopathic inflammatory diseases of the gastrointestinal tract and are a significant cause of morbidity worldwide. As yet, the etiology of IBD remains unclear, however it is hypothesised that in association with a disruption of the gastrointestinal epithelium, an initiator - believed to be either gastrointestinal microorganisms or their by-products - stimulates and subsequently drives a dysregulated immune response in genetically predisposed individuals.
Our laboratory is currently investigating the role of mucus-associated intestinal bacteria, including Helicobacter species and Campylobacter species in the initiation of CD in an attempt to better understand the mucosal events that occur in CD.
Investigation of the effect of Helicobacter pylori colonisation of the mouse stomach on subsequent colonisation of the intestine by non-pylori Helicobacter species.
The incidence of IBD is increasing worldwide. This increased incidence appears to be associated with increased socio-economic status, a finding that is in contrast to H. pylori infection, which is rapidly decreasing with increased socio-economic status. Based on current epidemiological trends and our studies in children, we hypothesise that gastric (stomach) H. pylori infection may have a protective effect against colonisation with non-pylori Helicobacter species in the intestines.
To test our hypothesis we will first infect mice with the H. pylori and then determine whether these mice are protected against colonisation by non-pylori Helicobacter species compared to mice not infected with the H. pylori. Techniques to be used include small animal handling, oral-gavage inoculation, bacterial cultivation, PCR, sequencing and examination of histological sections.
Investigation of intestinal colonisation by non-jejuni Campylobacter species in mice
Currently, the exact causative agent of IBD remains unknown. Recently, we detected a significantly higher prevalence of non-jejuni Campylobacter species in biopsies collected from children with CD compared with controls. Furthermore, we isolated four non-jejuni Campylobacter species from colonic biopsy samples of children with CD. Of these, C. concisus and C. showae are motile while C. hominis and B. ureolyticus are non-motile. As inflammatory responses in IBD occur at mucosal surfaces, we hypothesised that bacterial species with the ability to cross the thick intestinal mucus layer and colonise areas in close proximity to the intestinal epithelium are most likely to be involved in the initiation of IBD.
In this project, we will examine in mice the intestinal colonisation niche of the four Campylobacter species that we have isolated. Techniques to be used include small animal handling, bacterial cultivation, PCR and fluorescent in situ hybridization (FISH) /confocal microscopy.
BABS personnel that are responsible for this project
