Intermittent antibiotic treatment accelerated the development of colitis in IL-10 knockout mice

Abstract

Background and aimsMany epidemiological studies suggest an association between antibiotic exposure and the development of inflammatory bowel disease [IBD]. However, the majority of these studies are observational and still the question remains, “Does the specific antibiotic administration regimen play a role in the development of colitis?” This study aimed to compare the possible effects of continuous and intermittent antibiotic exposure on the development of colitis using a colitis-susceptible IL-10 knockout [IL-10–/–] mouse model. MethodsIL-10–/– mice [C57BL/6] were randomly assigned to a non-antibiotic group, continuous antibiotic group and intermittent antibiotic group, and observed for 30 weeks. The antibiotic cocktail was given via the drinking water. The differential response to antibiotics was assessed. ResultsIntermittent antibiotic treatment resulted in severe colitis with early disease onset in IL-10–/– mice. Higher unit colon weight and spleen weight were observed in intermittent antibiotic-treated mice but not in the continuous antibiotic group. Moreover, intermittent antibiotic treatment aggravated epithelial damage and colonic inflammation, mucosal barrier dysfunction and colonic allergic sensitization in IL-10–/– mice, whereas continuous antibiotic treatment ameliorated these symptoms. Male IL-10–/– mice with intermittent antibiotic exposure were more susceptible to colonic inflammation and allergic response than females. ConclusionsIn summary, intermittent antibiotic exposure accelerated the development of severe colitis more than continuous antibiotic exposure in IL-10–/– male mice. In addition to the colonic damage and impaired barrier function, stimulation of allergic response may play a role in accelerating the development of colitis in genetically susceptible mice.