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


ABSTRACT: 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.

SUBMITTER: Adami AJ 

PROVIDER: S-EPMC6258300 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Adami Alexander J AJ   Bracken Sonali J SJ   Guernsey Linda A LA   Rafti Ektor E   Maas Kendra R KR   Graf Joerg J   Matson Adam P AP   Thrall Roger S RS   Schramm Craig M CM  

Pediatric research 20180702 3


<h4>Introduction</h4>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.<h4>Methods</h4>Mice were exposed to three short courses of ABX following weaning and experimental asthma was thereafter induced. Airway cell counts and differentials; serum immunoglo  ...[more]

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