A291 INVESTIGATING THE ROLE OF ANTIBIOTICS AND ADHERENT-INVASIVE E. COLI IN THE PATHOGENESIS OF CROHN’S DISEASE

Crohn’s disease (CD) is an immune-mediated intestinal illness that is a significant health concern in many developed countries. CD is believed to have a complex etiology consisting of both host susceptibility factors and environmental insults. Multiple epidemiological studies have linked antibiotics with subsequent CD diagnosis. CD is also associated with increased abundance of an unusual phenotypic group of Escherichia coli known as adherent-invasive E. coli (AIEC) in many patients. AIEC are characterized by their ability to adhere and invade various cell types, to stimulate the production of inflammatory cytokines, and also tend to be resistant to multiple classes of antibiotics. Our lab has found that chronic colonisation of conventional mice with AIEC leads to intestinal inflammation and fibrosis. Our objective was to use this mouse model to investigate the impact of antibiotics on AIEC colonisation, pathology, and immune responses. Mice were treated with various antibiotics in drinking water or by oral gavage. These mice were infected with various doses of AIEC either before or after antibiotic treatment. We found that certain antibiotics administered prior to infection greatly reduced the infectious dose of bacteria required and led to greater bacterial burden. Mice administered antibiotics after infection similarly showed an expansion of AIEC in the feces and tissues. We are continuing to investigate how antibiotics alter AIEC colonisation by studying the metabolic and immune consequences of antibiotic treatment. These results show that antibiotics may create a favourable environment for AIEC colonisation in CD patients. Future work will continue investing how antibiotics impact the gut environment in the context of CD. CIHROntario Graduate Scholarship