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

ÖZKUL KOÇAK C., Ruiz V. E., Battaglia T., Xu J., Roubaud-Baudron C., Cadwell K., ...More

GENOME MEDICINE, vol.12, no.1, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 12 Issue: 1
  • Publication Date: 2020
  • Doi Number: 10.1186/s13073-020-00764-z
  • Journal Name: GENOME MEDICINE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, EMBASE, MEDLINE, Directory of Open Access Journals
  • Keywords: DSS-induced colitis, Gastrointestinal microbiota, Pulsed antibiotic treatment, Macrolide, Childhood antibiotic use, REGULATORY T-CELLS, CROHNS-DISEASE, GUT MICROBIOTA, MICE, COLONIZATION, EXPOSURE, INFLAMMATION, ASSOCIATION, ACTIVATION, CHILDREN
  • Hacettepe University Affiliated: Yes


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.