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Translational Investigation

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

Pediatric Research (2018) | Download Citation




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.


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.


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.


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.

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Category of Study: Translational


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We thank Jacqui Benjamino, Susan Janton, and Michael Nelson of the Graf Lab (UConn Storrs) for feedback and assistance. We also thank David Benson (UConn Storrs) for use of his laboratory space for experimentation. This work was supported by National Institutes of Health grants R01-AI43573 (R.S.T. and C.M.S.), F30-HL122018 (S.J.B.), and F30 HL-126324 (A.J.A.).

Author information


  1. Department of Immunology, University of Connecticut Health, Farmington, CT, USA

    • Alexander J. Adami
    • , Sonali J. Bracken
    • , Linda A. Guernsey
    • , Adam P. Matson
    •  & Roger S. Thrall
  2. Department of Pediatrics, University of Connecticut Health, Farmington, CT, USA

    • Linda A. Guernsey
    • , Ektor Rafti
    • , Adam P. Matson
    •  & Craig M. Schramm
  3. Microbial Analysis, Resources, and Services Facility, University of Connecticut, Storrs, CT, USA

    • Kendra R. Maas
  4. Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA

    • Joerg Graf
  5. Division of Neonatology, Connecticut Children’s Medical Center, Hartford, CT, USA

    • Adam P. Matson
  6. Division of Pulmonary Medicine, Connecticut Children’s Medical Center, Hartford, CT, USA

    • Craig M. Schramm


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The authors declare no competing interests.

Corresponding author

Correspondence to Craig M. Schramm.

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