Abstract
Broad-spectrum antibiotics are frequently prescribed to children. Early childhood represents a dynamic period for the intestinal microbial ecosystem, which is readily shaped by environmental cues; antibiotic-induced disruption of this sensitive community may have long-lasting host consequences. Here we demonstrate that a single pulsed macrolide antibiotic treatment (PAT) course early in life is sufficient to lead to durable alterations to the murine intestinal microbiota, ileal gene expression, specific intestinal T-cell populations, and secretory IgA expression. A PAT-perturbed microbial community is necessary for host effects and sufficient to transfer delayed secretory IgA expression. Additionally, early-life antibiotic exposure has lasting and transferable effects on microbial community network topology. Our results indicate that a single early-life macrolide course can alter the microbiota and modulate host immune phenotypes that persist long after exposure has ceased.
Highlights
Broad-spectrum antibiotics are frequently prescribed to children
To determine if a single antibiotic course introduced early in life is sufficient to lead to durable changes in both the microbiota and in the host, we compared the effect of exposing mice to a single pulsed antibiotic course (PAT1) vs a 3-course (PAT3) regimen (Fig. 1a)
Inter-group community variation was higher in both the PAT1 and PAT3 groups compared to control, indicating that the greatest effect was from the first antibiotic course (Fig. 1d, Supplementary Fig. 1b and Supplementary Table 2)
Summary
Broad-spectrum antibiotics are frequently prescribed to children. Early childhood represents a dynamic period for the intestinal microbial ecosystem, which is readily shaped by environmental cues; antibiotic-induced disruption of this sensitive community may have long-lasting host consequences. We demonstrate that a single pulsed macrolide antibiotic treatment (PAT) course early in life is sufficient to lead to durable alterations to the murine intestinal microbiota, ileal gene expression, specific intestinal T-cell populations, and secretory IgA expression. Early-life antibiotic exposure has lasting and transferable effects on microbial community network topology. The period between birth and 3 years of age is critical for the development of the intestinal microbiota[10] Factors such as delivery mode, diet and antibiotics have considerable effects on the stability, succession and resilience of the intestinal microbial community[11]. We show that even a single antibiotic course, given early in life, leads to profound and long-lasting immunological changes in mice, and that an altered microbiota with altered keystone taxa is both necessary and sufficient to explain these effects
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