Early-life antibiotics attenuate regulatory T cell generation and increase the severity of murine house dust mite-induced asthma

Pediatr Res. 2018 Sep;84(3):426-434. doi: 10.1038/s41390-018-0031-y. Epub 2018 Jul 2.


Introduction: Early-life exposure to antibiotics (ABX) has been linked to increases in asthma severity and prevalence in both children and laboratory animals. We explored the immunologic mechanisms behind this association using a mouse model of house dust mite (HDM)-induced asthma and early-life ABX exposure.

Methods: Mice were exposed to three short courses of ABX following weaning and experimental asthma was thereafter induced. Airway cell counts and differentials; serum immunoglobulin E (IgE); pulmonary function; lung histopathology; pulmonary regulatory T cells (Tregs); and the fecal microbiome were characterized following ABX exposure and induction of experimental asthma.

Results: Asthma severity was increased in mice exposed to ABX, including: airway eosinophilia, airway hyper-reactivity, serum HDM-specific IgE, and lung histopathology. ABX treatment led to sharp reduction in fecal microbiome diversity, including the loss of pro-regulatory organisms such as Lachnospira. Pulmonary Tregs were reduced with ABX treatment, and this reduction was directly proportional to diminished microbiome diversity.

Conclusion: Intermittent exposure to ABX early in life worsened the severity of experimental asthma and reduced pulmonary Tregs; the latter change correlated with decreased microbiome diversity. These data may suggest targets for immunologic or probiotic therapy to counteract the harmful effects of childhood ABX.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Airway Remodeling
  • Allergens / immunology
  • Animals
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / pharmacology
  • Asthma / epidemiology*
  • Asthma / etiology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Feces / microbiology
  • Female
  • Immunoglobulin E / blood
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Microbiota
  • Prevalence
  • Pyroglyphidae*
  • RNA, Ribosomal, 16S / genetics
  • Respiratory Function Tests
  • T-Lymphocytes, Regulatory / cytology*
  • Th2 Cells / cytology


  • Allergens
  • Anti-Bacterial Agents
  • Cytokines
  • RNA, Ribosomal, 16S
  • Immunoglobulin E