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

Ceren Ozkul,Thomas Battaglia,Ken Cadwell,Claire Roubaud-Baudron,Victoria E Ruiz,Joseph Xu,Guillermo I Perez-Perez,Martin J Blaser

doi:10.1186/s13073-020-00764-z

Abstract

BackgroundThere 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).MethodsBy 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.ResultsA 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.ConclusionsThe findings in this experimental model provide evidence that early-life microbiota perturbation may increase risk of colitis later in life.

Highlights

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
We aimed to determine whether exposure to a single antibiotic course early-in-life would increase the severity of the experimental colitis induced in mice by dextran sodium sulfate (DSS) challenge
At P25, after the pups had been weaned, they were given DSS in their drinking water for 7 days; clinical consequences were assessed by evaluating weight change, fecal blood, and stool consistency scores and summarized by the disease activity index (DAI) (Fig. 1a–d; Additional file 1: Fig. S1A-G)

Summary

Introduction

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). Clinical studies have suggested the relationship of early-life gut microbiota with progression and severity of inflammatory conditions such as allergies, asthma, and inflammatory bowel disease (IBD) [5,6,7]. The majority of antibacterial drugs prescribed to children are for the treatment of common pediatric conditions such as upper respiratory tract infections, pharyngitis, and bronchitis that largely do not benefit from antibiotic therapy [12].

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