Abstract

Several studies have reported that gut and lung microbiomes are involved in the process of asthma pathogenesis. However, it remains unclear how perinatal or early-life antibiotic intervention affect adult allergic airway inflammation. We assigned C57BL/6 mice randomly to four experimental groups: normal saline control (NS), ovalbumin (OVA), vancomycin pretreated NS (VAN-NS), and vancomycin pretreated OVA (VAN-OVA). The vancomycin groups were orally given the drug from gestational day 14 to 6 week. An OVA-induced asthma model was then established at 6 weeks of age, and airway inflammation was evaluated. In addition, total DNA was extracted from the feces and lung tissue and used for 16S rDNA gene sequencing, to detect the composition of the microbiome. In the VAN-OVA group, airway inflammation and Th2-related cytokines were found to be significantly increased versus the control groups. Gene sequencing showed that vancomycin treatment attenuated the richness and evenness, and altered the composition of the microbiome in the gut and lung. Micrococcaceae and Clostridiaceae-1 were potentially correlated to the severity of allergic airway inflammation. Our study suggests that perinatal and early-life vancomycin intervention aggravates allergic inflammation in adulthood, which might be correlated with imbalanced gut and lung microbiome homeostasis.

Highlights

  • Asthma is defined as an allergen-induced chronic airway inflammation disease, characteristic of airway hyperresponsiveness (AHR), reversible airflow restriction, and airway remodeling

  • Our study suggests that perinatal and early-life vancomycin intervention aggravates allergic inflammation in adulthood, which might be correlated with imbalanced gut and lung microbiome homeostasis

  • To clarify the effect of antibiotics in early life on asthma, we established the following models: mice being exposed to vancomycin from late pregnancy to 6 weeks of age, when an OVAinduced asthma model was established (Figure 1A)

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Summary

Introduction

Asthma is defined as an allergen-induced chronic airway inflammation disease, characteristic of airway hyperresponsiveness (AHR), reversible airflow restriction, and airway remodeling. The clinical symptoms include coughing, wheezing, dyspnea, and chest tightness. Asthma is thought to be caused by a combination of genetic and environmental factors [1]. Several internal factors in the microbiome have been shown to play an important role in the pathogenesis of asthma [2]. Whether infections or exposure to microorganisms, the changes in the host microbiome composition are related to asthma development [3, 4]. Personal hygiene improvement and declining family size reduce early-life microbiome exposure are associated with an increased risk of atopic diseases [5]

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