Reduced mucosal antimicrobial activity in Crohn's disease of the colon

Sabine Nuding ^1*, Klaus Fellermann ², Jan Wehkamp ¹ and Eduard F Stange ²

¹ Dr. Margarete Fischer-Bosch-Institute for Clinical Pharmacology Stuttgart, Germany
² Robert-Bosch-Hospital Stuttgart, Germany

^* To whom correspondence should be addressed. E-mail: sabine.nuding{at}ikp-stuttgart.de.

Accepted 11 April 2007

Abstract

Objectives: In order to maintain the mucosal barrier against luminal microorganisms the intestinal epithelial cells synthesise various broad-spectrum antimicrobial peptides including defensins and cathelicidins. Recent studies indicate that both may be deficient in Crohn's disease. To elucidate possible functional consequences of this deficiency we investigated the antimicrobial activity in colonic mucosa from patients with inflammatory bowel disease and healthy controls.

Methods: We established a flow cytometric assay to quantitate bacterial killing and tested the antibacterial activity of cationic peptide extracts from colonic biopsies taken from patients with active or inactive ileocolonic or colonic Crohn's disease (n=22), ulcerative colitis (n=29) and controls (n=13) against clinical isolates of Bacteroides vulgatus and Enterococcus faecalis or the reference strains Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923.

Results: Compared with controls and ulcerative colitis there was a reduced antimicrobial effect in Crohn's disease extracts which was most evident against Bacteroides vulgatus. The antimicrobial effect against Escherichia coli and Enterococcus faecalis was significantly lower in Crohn's disease compared to ulcerative colitis. Activity against Staphylococcus aureus disclosed a similar pattern although less pronounced. The differences were independent from the inflammation status or concurrent steroid treatment. Bacteria incubated with biopsy extracts from ulcerative colitis patients showed frequently a characteristic change in cell size and granularity, compatible with more extensive membrane disintegration, compared with bacteria incubated with extracts from controls or Crohn's disease.

Conclusion: Crohn's disease of the colon is characterized by a diminished functional antimicrobial activity which is consistent with the reported low antibacterial peptide expression.

Keywords: Crohn's disease, antimicrobial activity, colon, defensins, flow cytometry

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