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A single early-in-life macrolide course has lasting effects on murine microbial network topology and immunity

Victoria E Ruiz1, Thomas Battaglia1, Zachary D Kurtz1

  • 1Departments of Medicine and Microbiology, New York University School of Medicine (NYUSM), New York, NY, 10016, USA.

Nature Communications
|September 13, 2017
PubMed

Insights

A single course of macrolide antibiotics in early life permanently alters the gut microbiota in mice. This disruption impacts the immune system, with lasting and transferable effects on host health.

Area of Science:

  • Microbiology
  • Immunology
  • Pediatric Health

Background:

  • Antibiotics are commonly prescribed to children, potentially disrupting the developing gut microbiome.
  • Early childhood is a critical window for microbial ecosystem development, sensitive to environmental factors.

Purpose of the Study:

  • To investigate the long-term effects of a single early-life macrolide antibiotic treatment (PAT) on the murine gut microbiota and host immune system.
  • To determine if the altered microbiota is necessary and sufficient for observed host effects.

Main Methods:

  • Administered a single pulsed macrolide antibiotic treatment (PAT) to young mice.
  • Analyzed changes in the intestinal microbiota composition and network topology.
  • Assessed ileal gene expression and specific intestinal T-cell populations.
  • Evaluated secretory IgA expression.

Main Results:

  • A single PAT course induced durable alterations in the murine intestinal microbiota.
  • Host immune phenotypes, including T-cell populations and secretory IgA, were persistently modulated.
  • The PAT-perturbed microbial community was necessary for host effects and sufficient to transfer delayed secretory IgA expression.
  • Lasting and transferable effects on microbial community network topology were observed.

Conclusions:

  • Early-life macrolide exposure causes long-lasting changes to the gut microbiota.
  • These microbial alterations modulate host immune phenotypes that persist beyond the antibiotic treatment period.
  • The gut microbiota plays a crucial role in mediating the long-term immune consequences of early-life antibiotic exposure.

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