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Antibiotics with a selective aerobic or anaerobic spectrum have different therapeutic activities in various regions of the colon in interleukin 10 gene deficient mice
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  1. F Hoentjen1,
  2. H J M Harmsen3,
  3. H Braat4,
  4. C D Torrice2,
  5. B A Mann2,
  6. R B Sartor2,
  7. L A Dieleman2
  1. 1Department of Gastroenterology, Free University Amsterdam, The Netherlands, and Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, USA.
  2. 2Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, USA
  3. 3Department of Medical Microbiology, University of Groningen, the Netherlands
  4. 4Department of Experimental Internal Medicine, Academic Medical Centre, Amsterdam, the Netherlands
  1. Correspondence to:
    Dr F Hoentjen
    Department of Medicine, Division of Digestive Diseases, Biomolecular Research Building, Rm 7331, CB 7032, UNC-Chapel Hill, Chapel Hill, NC 27599-7032, USA; frankhoentjenmed.unc.edu

Abstract

Background and aims: Multiple rodent models implicate resident intestinal bacteria in the pathogenesis of chronic immune mediated intestinal inflammation. Specific pathogen free (SPF) interleukin 10 gene deficient (IL-10−/−) mice develop colitis, which does not occur in the germ free (GF) state. We investigated whether broad or narrow spectrum antibiotics affect onset and progression of disease in various regions of IL-10−/− mice.

Methods: Metronidazole, ciprofloxacin, vancomycin-imipenem (50 mg/kg/day), or water (control) was administered orally before (prevention) or two weeks after (treatment) colonisation of GF IL-10−/− mice with SPF bacteria. After four weeks, colonic histology scores and cytokine production by colonic explants were determined. Caecal and colonic contents were collected for quantitative bacterial analysis.

Results: In the prevention study, all antibiotics decreased inflammation in the caecum and colon. However, in the treatment study, ciprofloxacin and vancomycin-imipenem decreased caecal inflammation, and reduced Escherichia coli and Enterococcus faecalis concentrations, whereas only vancomycin-imipenem lowered direct microscopic bacterial counts. In contrast, metronidazole and vancomycin-imipenem reduced colonic injury and eliminated anaerobic bacteria, including Bacteroides spp.

Conclusions: Both narrow and broad spectrum antibiotics can prevent disease but treatment of established colitis is more selective. Ciprofloxacin is most effective in the treatment of caecal inflammation, metronidazole preferentially treats the colon, whereas vancomycin-imipenem definitively treats both regions. These results suggest that subsets of aerobic or anaerobic bacteria show regional differences in their capacity to mediate experimental colitis in IL-10−/− mice.

  • antibiotics
  • bacteria
  • colitis
  • cytokines
  • interleukin 10
  • mice
  • CFU, colony forming units
  • FISH, fluorescent in situ hybridisation
  • GF, germ free
  • IBD, inflammatory bowel diseases
  • IL, interleukin
  • IL-10−/−, interleukin 10 gene deficient
  • MLN, mesenteric lymph node
  • SPF, specific pathogen free
  • TG, transgenic
  • TH1, T helper 1
  • DSS, dextran sulphate sodium
  • PBS, phosphate buffered saline
  • DAPI, diamidino-2-phenylindole
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