Background

Lower respiratory tract infections (LRTI) are a driving factor for pulmonary exacerbations and lung function decline in people with cystic fibrosis (CF). It was shown that the respiratory microbiota is closely related to the pathogenesis of LRTIs in healthy infants, but data in infants with CF is scarce.

Objectives

We aimed to study whether the early-life upper respiratory tract microbiota is associated with the occurrence, severity and frequency of respiratory symptoms in infants with CF.

Methods

16S rRNA gene V4 sequencing and subsequent analysis of the respiratory microbiota in biweekly nasal swabs in 50 infants with CF and 30 healthy controls from two prospective birth cohorts followed throughout the first year of life was performed. We assessed respiratory symptoms, antibiotic treatment and changes in the environment at time of swab via standardized telephone interviews.

Results

We analyzed 1511 time points (963 in CF). A lower ?-diversity (measured via Shannon diversity index) of the respiratory microbiota was associated with a higher number of LRTIs (Coef -0.42; 95% CI -0.59,-0.20; p<0.0001) in infants with CF. This lower ?-diversity was already present before first respiratory symptoms occurred (Coef -0.47; 95% CI -0.82,-0.12; p=0.01) and associations were robust when stratified for antibiotic treatment.  

Conclusion

Imbalanced respiratory microbiota profiles in early infancy might predispose additionally to susceptibility towards more frequent LRTIs in infants with CF independent of antibiotic treatment. A more diverse microbiota in early life in CF might play a role in prevention of later disease progression and could be considered as a future therapeutic target.