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Published on: May 2, 2018
Induction of colonic transmural inflammation by Bacteroides fragilis: implication of matrix metalloproteinases
Carlos Medina1, Alfredo Santana, Marta Llopis
1Gastroenterology Department and Research Unit, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain. cmedinammar@hotmail.com
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.
Insights
Bacteroides fragilis metalloproteinases (MMPs) contribute to transmural inflammation in the gut. Inhibiting bacterial MMPs reduced inflammation, suggesting their role in intestinal disease pathogenesis.
Area of Science:
- Microbiology
- Gastroenterology
- Immunology
Background:
- Commensal bacteria play a role in intestinal inflammation.
- The exact mechanisms of bacterial involvement in gut inflammation remain unclear.
- Bacteroides fragilis-produced metalloproteinases (MMPs) are hypothesized to facilitate bacterial migration and transmural inflammation.
Purpose of the Study:
- To investigate the role of bacterial MMP activity in an experimental model of colitis.
- To determine if MMP inhibition affects bacterial translocation and inflammation.
Main Methods:
- Intramural injection of viable B. fragilis or Escherichia coli into the colonic wall of rats.
- Administration of the MMP inhibitor phenanthroline to assess its effect on lesion scores.
- Measurement of MMP activity in bacterial suspensions using an azocoll assay.
Main Results:
- B. fragilis inoculation induced chronic, subserosal inflammatory lesions, while E. coli caused acute, widespread inflammation.
- Phenanthroline treatment significantly reduced subserosal lesion scores in B. fragilis-inoculated rats.
- B. fragilis suspensions exhibited MMP activity, unlike E. coli. Sonication reduced B. fragilis MMP activity and virulence.
Conclusions:
- Bacterial MMPs are implicated in the serosal migration of B. fragilis.
- Bacterial MMPs may contribute to the induction of transmural inflammation in the colon.
- Targeting bacterial MMPs could be a therapeutic strategy for intestinal inflammation.
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