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A single early-in-life antibiotic course increases susceptibility to DSS-induced colitis

Abstract : Background: There is increasing evidence that the intestinal microbiota plays a crucial role in the maturation of the immune system and the prevention of diseases during childhood. Early-life short-course antibiotic use may affect the progression of subsequent disease conditions by changing both host microbiota and immunologic development. Epidemiologic studies provide evidence that early-life antibiotic exposures predispose to inflammatory bowel disease (IBD). Methods: By using a murine model of dextran sodium sulfate (DSS)-induced colitis, we evaluated the effect on disease outcomes of early-life pulsed antibiotic treatment (PAT) using tylosin, a macrolide and amoxicillin, a beta-lactam. We evaluated microbiota effects at the 16S rRNA gene level, and intestinal T cells by flow cytometry. Antibiotic-perturbed or control microbiota were transferred to pups that then were challenged with DSS. Results: A single PAT course early-in-life exacerbated later DSS-induced colitis by both perturbing the microbial community and altering mucosal immune cell composition. By conventionalizing germ-free mice with either antibiotic-perturbed or control microbiota obtained 40 days after the challenge ended, we showed the transferrable and direct effect of the still-perturbed microbiota on colitis severity in the DSS model. Conclusions: The findings in this experimental model provide evidence that early-life microbiota perturbation may increase risk of colitis later in life.
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Contributor : Claire Roubaud-Baudron Connect in order to contact the contributor
Submitted on : Tuesday, November 17, 2020 - 3:29:46 PM
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Ceren Ozkul, Victoria Ruiz, Thomas Battaglia, Joseph Xu, Claire Roubaud-Baudron, et al.. A single early-in-life antibiotic course increases susceptibility to DSS-induced colitis. Genome Medicine, BioMed Central, 2020, 12 (1), pp.65. ⟨10.1186/s13073-020-00764-z⟩. ⟨inserm-03010073⟩



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