Induction of colonic transmural inflammation by Bacteroides fragilis: Implication of matrix metalloproteinases

Abstract

Background Commensal bacteria are implicated in the pathophysiology of intestinal inflammation, but the precise pathogenetic mechanisms are not known. We hypothesized that Bacteroides fragilis-produced metalloproteinases (MMPs) are responsible for bacterial migration through the intestinal wall and transmural inflammation. Aim To investigate the role of bacterial-MMP activity in an experimental model of colitis induced by the intramural injection of bacteria. Methods Suspensions of viable B. fragilis or Escherichia coli were injected into the colonic wall, and the effect of the MMP inhibitor (phenantroline) on histologic lesion scores was tested. MMP activity in bacterial suspensions was measured by azocoll assay. Results The inoculation with B. fragilis induced chronic inflammatory lesions that were preferentially located in the subserosa, whereas inoculation with E. coli induced acute-type inflammatory reactions, evenly distributed in both the submucosa and subserosa. Treatment with phenantroline significantly decreased subserosal lesion scores in rats inoculated with B. fragilis, but not in rats inoculated with E. coli. Bacterial suspensions of B. fragilis showed MMP activity, but E. coli suspensions did not. Sonication of B. fragilis reduced MMP activity and virulence to induce serosal lesions. Conclusion Our data suggest that bacterial MMPs may be implicated in the serosal migration of B. fragilis and in the induction of transmural inflammation.