Longitudinal development of the airway microbiota in infants with cystic fibrosis

Bushra Ahmed,Miriam F Moffatt,Michael J Cox,Leah Cuthbertson,William O C Cookson,Andrew Bush,Phillip James,Jane C Davies

doi:10.1038/s41598-019-41597-0

Bushra Ahmed, Miriam F Moffatt + Show 6 more

Open Access

https://doi.org/10.1038/s41598-019-41597-0

Copy DOI

Abstract

The pathogenesis of airway infection in cystic fibrosis (CF) is poorly understood. We performed a longitudinal study coupling clinical information with frequent sampling of the microbiota to identify changes in the airway microbiota in infancy that could underpin deterioration and potentially be targeted therapeutically. Thirty infants with CF diagnosed on newborn screening (NBS) were followed for up to two years. Two hundred and forty one throat swabs were collected as a surrogate for lower airway microbiota (median 35 days between study visits) in the largest longitudinal study of the CF oropharyngeal microbiota. Quantitative PCR and Illumina sequencing of the 16S rRNA bacterial gene were performed. Data analyses were conducted in QIIME and Phyloseq in R. Streptococcus spp. and Haemophilus spp. were the most common genera (55% and 12.5% of reads respectively) and were inversely related. Only beta (between sample) diversity changed with age (Bray Curtis r2 = 0.15, P = 0.03). Staphylococcus and Pseudomonas were rarely detected. These results suggest that Streptococcus spp. and Haemophilus spp., may play an important role in early CF. Whether they are protective against infection with more typical CF micro-organisms, or pathogenic and thus meriting treatment needs to be determined.

Highlights

Respiratory infections begin early in cystic fibrosis (CF) even in the absence of symptoms[1]
Due to being opportunistic, sampling frequency varied (Supplementary Fig. S1a) and samples were clustered into age ranges (e.g. 3–4 months etc.) (Supplementary Fig. S1b)
In this study we have shown that the airway microbiota in CF infants is highly individual and develops gradually over the first two years of life

Summary

Introduction

Respiratory infections begin early in CF even in the absence of symptoms[1]. More frequent exacerbations before 2 years of age are associated with reduced forced expiratory volume in one second (FEV1) at 5 years[2]. Nasopharyngeal samples, used to track changes in the airway microbiota in the first year of life, have demonstrated differences between CF infants and controls, with Staphylococcus spp. and Streptococcus spp. more prevalent in CF and Haemophilus spp. and Prevotella spp. more prevalent in controls[12]. Studies comparing nasopharyngeal sampling with sputum, have shown significant differences in both community diversity and composition between these two respiratory samples in children with CF13. Larger data sets, coupling detailed clinical information with frequent sampling, are needed to better understand the progression of the CF airway microbiota. This present study aimed to describe how the CF infant microbiota develops over the first two years of life

Methods

Results

Conclusion