An observational study of the lung microbiome and lung function in young children with cystic fibrosis across two countries with differing antibiotic practices

Background: Cystic fibrosis (CF) lung disease begins early, and prophylactic antibiotics have been used to prevent Staphylococcus aureus infection. This study examined the lung microbiome in two countries with differing antibiotic practices and its relationship to lung function in young children with CF. Methods: A binational, longitudinal, observational study was performed to define the lower airway microbiome in infants with CF. 16S rRNA sequencing was performed using lavage fluid to characterize the lung microbiota in 45 infants with and without prophylactic antibiotic therapy at an average age of approximately 3 months and 14 months. The association between pulmonary function, bacterial community diversities, and taxa was assessed. Results: Expected CF bacterial genera and non-traditional bacteria, such as Streptococcus, were identified as core taxa. Microbial community shifts were observed in infants who received antibiotic prophylaxis, with lower alpha diversity (ANOVA, P < 0.05) and a higher proportion of Streptococcus at the first visit. Beta diversity (FEV_0.5z; MiRKAT, P < 0.05) and Streptococcus were associated with FEV_0.5z (LASSO and linear regression, β < 0). Functional annotation suggested that alteration of lung microbiota may be linked to antimicrobial resistance. Conclusions: Lung microbial diversity in infants with CF varied between the two countries, particularly during early infancy. A shift in the lung microbiome toward a higher relative abundance of Streptococcus was associated with reduced pulmonary function.