期刊
GENOME MEDICINE
卷 12, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13073-020-00764-z
关键词
DSS-induced colitis; Gastrointestinal microbiota; Pulsed antibiotic treatment; Macrolide; Childhood antibiotic use
资金
- NIH [U01 A122285]
- Scientific and Technological Research Council of Turkey (TUBITAK) International Research Fellowship Programme
- Sergei S. Zlinkoff Fund
- CD Research Fund
- Transatlantic Network of the Fondation Leducq
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据