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

Genome Med. 2020 Jul 25;12(1):65. doi: 10.1186/s13073-020-00764-z.

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.

Keywords: Childhood antibiotic use; DSS-induced colitis; Gastrointestinal microbiota; Macrolide; Pulsed antibiotic treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Anti-Bacterial Agents / adverse effects*
  • Biodiversity
  • Colitis / etiology*
  • Colitis / metabolism
  • Colitis / pathology
  • Dextran Sulfate / adverse effects
  • Disease Models, Animal
  • Disease Susceptibility*
  • Dysbiosis / complications
  • Dysbiosis / etiology
  • Gastrointestinal Microbiome / drug effects
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Mice
  • Permeability
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism

Substances

  • Anti-Bacterial Agents
  • Dextran Sulfate