Antibiotic therapy attenuates colitis in interleukin 10 gene-deficient mice.
OBJECTIVE
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.
Madsen
K L
KL
Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Doyle
J S
JS
Tavernini
M M
MM
Jewell
L D
LD
Rennie
R P
RP
Fedorak
R N
RN
D000367:Age Factors; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001439:Bacteroides / Q000187:drug effects / Q000254:growth & development; D002939:Ciprofloxacin / Q000494:pharmacology*; D003013:Clostridium / Q000187:drug effects / Q000254:growth & development; D003092:Colitis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004755:Enterobacteriaceae / Q000187:drug effects / Q000254:growth & development*; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016983:Enterococcus / Q000187:drug effects / Q000254:growth & development; D016753:Interleukin-10 / Q000235:genetics*; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D007778:Lactobacillus / Q000187:drug effects / Q000254:growth & development; D008137:Longitudinal Studies; D008795:Metronidazole / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009355:Neomycin / Q000494:pharmacology; D013291:Streptococcus / Q000187:drug effects / Q000254:growth & development
D000900:Anti-Bacterial Agents; D016753:Interleukin-10; D008795:Metronidazole; D002939:Ciprofloxacin; D009355:Neomycin