Antibiotic therapy attenuates colitis in interleukin 10 gene–deficient mice

KL Madsen, JS Doyle, MM Tavernini, LD Jewell… - Gastroenterology, 2000 - Elsevier
KL Madsen, JS Doyle, MM Tavernini, LD Jewell, RP Rennie, RN Fedorak
Gastroenterology, 2000Elsevier
Background & Aims: Interleukin (IL)-10 gene–deficient mice, raised under germfree
conditions, do not develop colitis, implying a role for bacteria. This study mapped the
appearance of luminal colonic bacteria and, using antibiotic treatment, determined their
association with colitis in IL-10 gene–deficient mice. Methods: Mice were treated with
ciprofloxacin or with neomycin and metronidazole. The intestine was harvested for
histological scoring and bacterial assessment. Results: At 2 weeks of age, before the …
Background & Aims
Interleukin (IL)-10 gene–deficient mice, raised under germfree conditions, do not develop colitis, implying a role for bacteria. This study mapped the appearance of luminal colonic bacteria and, using antibiotic treatment, determined their association with colitis in IL-10 gene–deficient mice.
Methods
Mice were treated with ciprofloxacin or with neomycin and metronidazole. The intestine was harvested for histological scoring and bacterial assessment.
Results
At 2 weeks of age, before the development of colitis, IL-10 gene–deficient mice demonstrated an earlier appearance of Streptococcus and Clostridium sp., and had a greater proportion (P < 0.01) of bacteria adherent to the colonic mucosa. This pattern of increased adherent bacteria persisted for the 12 weeks of study. Treatment of mice before the onset of colonic inflammation, with either antibiotic regime, reduced mucosal adherent bacteria and prevented colitis (P < 0.01). In contrast, treatment of established colitis with neomycin and metronidazole did not reduce adherent bacterial levels, yet was more efficacious (P < 0.05) in treating established colitis than ciprofloxacin, which did reduce adherent colonic bacteria.
Conclusions
In the IL-10 gene–deficient mouse model, the appearance and number of mucosal adherent colonic bacteria are altered before the onset of colitis. Antibiotics both prevent and treat the colitis through correction of this primary bacterial alteration. GASTROENTEROLOGY 2000;118:1094-1105
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