Early-life vancomycin treatment promotes airway inflammation and impairs microbiome homeostasis

Aging (Albany NY). 2019 Apr 13;11(7):2071-2081. doi: 10.18632/aging.101901.

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.

Keywords: allergic airway inflammation; asthma; eosinophil; microbiome; vancomycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / administration & dosage
  • Animals
  • Animals, Newborn
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Asthma / etiology*
  • Asthma / microbiology
  • Asthma / pathology
  • Disease Models, Animal
  • Female
  • Homeostasis
  • Inflammation / etiology
  • Inflammation / microbiology
  • Inflammation / pathology
  • Lung / drug effects
  • Lung / microbiology
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microbiota / drug effects*
  • Microbiota / genetics
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / etiology
  • Prenatal Exposure Delayed Effects / microbiology
  • Prenatal Exposure Delayed Effects / pathology
  • RNA, Ribosomal, 16S / genetics
  • Vancomycin / administration & dosage
  • Vancomycin / adverse effects*

Substances

  • Allergens
  • Anti-Bacterial Agents
  • RNA, Ribosomal, 16S
  • Vancomycin
  • Ovalbumin