Progression of the bronchoalveolar lavage microbiome and disease markers in pre-school children with Cystic Fibrosis

A polymicrobial infection with well-known pathogens characterizes established CF lung disease. Few data describe lower airway infection in pre-school CF children. We hypothesize that aspiration of oral flora shapes the CF lung microbiome with subsequent emergence of established pathogens, and these changes in microbial composition are associated with airways inflammation and structural disease. Microbial characterisation using 16S DNA sequencing was performed in 53 right middle lobe bronchoalveolar lavage (BAL) samples obtained from 46 children ages 3-60 months undergoing CT and BAL as part of the Australian Respiratory Early Surveillance Team. Twenty-three genera, with an abundance of =0.5%, clustered into environmental, oral, and defined-pathogenic bacteria. Children <2 years exhibited predominantly environmental and oral bacterial clusters whereas older children exhibited pathogens. Clinical phenotypes differed depending on the dominant bacterial cluster-those dominated by environmental taxa showed least and those with pathogens most inflammation and CT-changes. Bacterial richness and diversity decreased across the three clusters. Subjects with prior BAL documented pathogens revealed negative associations of bacterial richness and diversity with markers of lung disease. The microbial community in early CF is highly diverse and shaped by oral flora in the presence of structural lung disease. Subsequent pathogen acquisition is associated with decreased diversity and increased inflammation.