Volume 118, Issue 6, Pages 1094-1105 (June 2000) Antibiotic therapy attenuates colitis in interleukin 10 gene–deficient mice  Karen L. Madsen, Jason S. Doyle, Michele M. Tavernini, Lawrence D. Jewell, Robert P. Rennie, Richard N. Fedorak  Gastroenterology  Volume 118, Issue 6, Pages 1094-1105 (June 2000) DOI: 10.1016/S0016-5085(00)70362-3 Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 1 (A) Total bacteria and (B) adherent or translocated bacteria in the colons of control (■) and IL-10 gene–deficient mice (▨) as a function of age. IL-10 gene–deficient mice had significantly greater levels of colonic mucosal adherent or translocated bacteria than age-matched controls at all ages. In contrast, total colonic bacterial levels were reduced in IL-10 gene–deficient mice at 2 and 4 weeks of age.*P < 0.01 compared with age-matched controls; n = 6-8 animals in each group. Gastroenterology 2000 118, 1094-1105DOI: (10.1016/S0016-5085(00)70362-3) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 2 IL-10 gene–deficient mice treated with antibiotics from birth to 4 or 8 weeks of age and then assessed at 4 or 8 weeks of age, respectively. (A) Histological colonic injury, (B) total colonic bacteria levels, (C) adherent or translocated bacteria levels, and (D) Lactobacillus sp. levels in colons of control mice (■), IL-10 gene–deficient mice (▨), and IL-10 gene–deficient mice receiving either neomycin-metronidazole (85 ± 2 to 145 ± 3 mg · kg−1 · day−1; ▧) or ciprofloxacin (42 ± 2 mg · kg−1 · day−1; ●) continuously from birth to 4 or 8 weeks of age. Neomycin-metronidazole administration completely prevented colitis in association with normalization of total, mucosal adherent or translocated, and Lactobacillus sp. bacteria to control levels. Ciprofloxacin administration also completely prevented colitis in association with levels of total, adherent or translocated, and Lactobacillus sp. bacterial levels to below control values. *P < 0.05 compared with control mice; +P < 0.05 compared with IL-10 gene–deficient mice. Gastroenterology 2000 118, 1094-1105DOI: (10.1016/S0016-5085(00)70362-3) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 3 IL-10 gene–deficient mice treated with antibiotics from birth to 4 weeks of age, at which time treatment was stopped, and mice were assessed at 8 weeks of age. (A) Histological colonic injury, (B) total colonic bacteria levels, (C) adherent or translocated bacteria levels, and (D) Lactobacillus sp. levels in colons of control mice (■), IL-10 gene–deficient mice (▨), and IL-10 gene–deficient mice receiving either neomycin-metronidazole (85 ± 2 to 145 ± 3 mg · kg−1 · day−1; ▧) or ciprofloxacin (42 ± 2 mg · kg−1 · day−1; ●) continuously from birth to 4 weeks of age, at which time the antibiotics were stopped. Mice were then assessed at 8 weeks of age. Neomycin-metronidazole administration prevented colitis in association with normalization of mucosal adherent or translocated bacteria and Lactobacillus sp. levels. Ciprofloxacin administration also prevented colitis in association with levels of adherent or translocated bacteria and Lactobacillus sp. to below control values. *P < 0.05 compared with control mice; +P < 0.05 compared with IL-10 gene–deficient mice. n = 6-8 animals in each group. Gastroenterology 2000 118, 1094-1105DOI: (10.1016/S0016-5085(00)70362-3) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 4 IL-10 gene–deficient mice with established colitis treated with antibiotics between 8 and 12 weeks of age and then assessed at 12 weeks of age. (A) Histological colonic injury, (B) total colonic bacteria levels, (C) adherent or translocated bacteria levels, (D) and Lactobacillus sp. levels in colons of control mice (■), IL-10 gene–deficient mice (▨), and IL-10 gene–deficient mice with established colitis receiving either neomycin-metronidazole (85 ± 2 to 145 ± 3 mg · kg−1 · day−1; ▧) or ciprofloxacin (42 ± 2 mg · kg−1 · day−1; ●) between 8 and 12 weeks of age. Neomycin-metronidazole administration attenuated existing colitis in association with an increase in Lactobacillus sp., with no change in total or mucosal adherent or translocated bacterial levels. Ciprofloxacin administration mildly attenuated existing colitis without an increase in Lactobacillus sp. levels, but with decreases in total and mucosal adherent or translocated bacteria levels. *P < 0.05 compared with control mice; +P < 0.05 compared with IL-10 gene–deficient mice. n = 6-8 animals in each group. Gastroenterology 2000 118, 1094-1105DOI: (10.1016/S0016-5085(00)70362-3) Copyright © 2000 American Gastroenterological Association Terms and Conditions