Abstract
The cystic fibrosis (CF) lung microbiome has been studied in children and adults; however, little is known about its relationship to early disease progression. To better understand the relationship between the lung microbiome and early respiratory disease, we characterized the lower airways microbiome using bronchoalveolar lavage (BAL) samples obtained from clinically stable CF infants and preschoolers who underwent bronchoscopy and chest computed tomography (CT). Cross-sectional samples suggested a progression of the lower airways microbiome with age, beginning with relatively sterile airways in infancy. By age two, bacterial sequences typically associated with the oral cavity dominated lower airways samples in many CF subjects. The presence of an oral-like lower airways microbiome correlated with a significant increase in bacterial density and inflammation. These early changes occurred in many patients, despite the use of antibiotic prophylaxis in our cohort during the first two years of life. The majority of CF subjects older than four harbored a pathogen dominated airway microbiome, which was associated with a further increase in inflammation and the onset of structural lung disease, despite a negligible increase in bacterial density compared to younger patients with an oral-like airway microbiome. Our findings suggest that changes within the CF lower airways microbiome occur during the first years of life and that distinct microbial signatures are associated with the progression of early CF lung disease.
Highlights
Cystic fibrosis (CF) is a multisystem genetic disease in which pulmonary manifestations account for the majority of morbidity and mortality
To understand the evolution of the CF lower airways microbiome, we applied sensitive molecular detection methods to characterize the bacterial DNA sequences in bronchoalveolar lavage (BAL) samples obtained from clinically stable infants and preschoolers who underwent bronchoscopy
Our findings demonstrate that CF infants have relatively sterile lower airways with a progressive shift to a microbiome dominated by aerobic and anaerobic bacterial species commonly associated with the oral cavity
Summary
Cystic fibrosis (CF) is a multisystem genetic disease in which pulmonary manifestations account for the majority of morbidity and mortality. Sensitive molecular based (16S rRNA gene sequencing) microbiome analysis of respiratory secretions from children and adults with CF suggest that infection is polymicrobial and often includes both traditional CF pathogens and aerobic and anaerobic bacteria typically found in the oral cavity [3,4,5,6,7,8]. Contamination of lower airways samples by oropharyngeal secretions during collection remains a significant concern in airway microbiome research [13]. Consistent with this concern, it has been shown that oral bacteria are abundant in sputum and throat swabs from end-stage CF patients immediately prior to lung transplant, but airway samples obtained directly from the explanted lungs immediately after transplant are dominated almost exclusively by traditional CF pathogens [14]
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