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

Abstract

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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