Divergence of bacterial communities in the lower airways of CF patients in early childhood

Abstract

Rationale Chronic airway infection and inflammation resulting in progressive, obstructive lung disease is the leading cause of morbidity and mortality in cystic fibrosis. Understanding the lower airway microbiota across the ages can provide valuable insight and potential therapeutic targets. Objectives To characterize and compare the lower airway microbiota in cystic fibrosis and disease control subjects across the pediatric age spectrum. Methods Bronchoalveolar lavage fluid samples from 191 subjects (63 with cystic fibrosis) aged 0 to 21 years were collected along with relevant clinical data. We measured total bacterial load using quantitative polymerase chain reaction and performed 16S rRNA gene sequencing to characterize bacterial communities with species-level sensitivity for select genera. Clinical comparisons were investigated. Measurements and main results Cystic fibrosis samples had higher total bacterial load and lower microbial diversity, with a divergence from disease controls around 2–5 years of age, as well as higher neutrophilic inflammation relative to bacterial burden. Cystic fibrosis samples had increased abundance of traditional cystic fibrosis pathogens and decreased abundance of the Streptococcus mitis species group in older subjects. Interestingly, increased diversity in the heterogeneous disease controls was independent of diagnosis and indication. Sequencing was more sensitive than culture, and antibiotic exposure was more common in disease controls, which showed a negative relationship with load and neutrophilic inflammation. Conclusions Analysis of lower airway samples from people with cystic fibrosis and disease controls across the ages revealed key differences in airway microbiota and inflammation. The divergence in subjects during early childhood may represent a window of opportunity for intervention and additional study.