3rd Annual BMRP Investigator Meeting - Abstract
Disrupted Barrier to Non-pathogenic E. coli in the Follicle-Associated Epithelium of Non-inflamed Ileum of Patients with Crohn’s Disease
Asa K. Velin1, Ann-Charlott Ericson1, Elisabet Gullberg2, Per Artursson2, Karl-Eric Magnusson3 and Johan D. Söderholm1,a
1Department of Biomedicine and Surgery, Linköping University (Linköping, Sweden); 2Department of Pharmacy, Uppsala University (Uppsala, Sweden); 3Department of Medical Microbiology, Linköping University (Linköping, Sweden)
The earliest visible signs of Crohn’s disease (CD) are microscopic erosions at the follicle-associated epithelium (FAE) covering Peyer’s patches. The FAE, with its enrichment in M cells, is important for regulation of mucosal immune responses and as a route of entry for micro-organisms. A technique to study mucosal barrier function of the human FAE has been established at our laboratory. Our aims in the present study were to assess the mucosal barrier to antigens and bacteria in ileal FAE of CD.
Surgical specimens of macroscopically normal ileum from ten patients with CD and 15 control patients were studied. Samples of FAE were identified and mounted in modified Ussing chambers. Mucosal barrier function was studied using 51Cr-EDTA and the protein antigen, horseradish peroxidase (HRP). Moreover, transmucosal uptake of two strains of non-pathogenic E. coli, chemically-killed fluorescent E. coli K-12, and live E. coli HB101 incorporated with green fluorescent protein (GFP), was determined. Passage routes were studied by confocal laser scanning microscopy. The FAE of CD showed significantly increased transmucosal passage of chemically-killed fluorescent E. coli K-12 as well as of live E. coli HB101 compared with FAE of control patients. Confocal microscopy revealed an increased number of intra- and subepithelial fluorescent bacteria in CD mucosa. FAE permeability to 51Cr-EDTA and HRP was equal in the patient groups.
Increased transmucosal passage of non-pathogenic E. coli in FAE of patients with CD suggests a previously unrecognized defect in the barrier to commensal bacteria in these specialized regions. Therefore, an increased cross-talk between luminal bacteria and the inductive sites of the mucosal immune system could take place in CD. This may have important implications for the understanding of the pathogenesis of ileal CD.
aPrincipal Investigator