Background Complex polymicrobial communities infect cystic fibrosis (CF) lower airways. Generally, communities with low diversity, dominated by classical CF pathogens, associate with worsened patient status at sample collection. However, it is not known if the microbiome can predict future outcomes. We sought to determine if the microbiome could be adapted as a biomarker for patient prognostication.
Methods We retrospectively assessed prospectively collected sputum from a cohort of 104 individuals aged 18–22 to determine factors associated with progression to early end-stage lung disease (eESLD; death/transplantation <25 years) and rapid pulmonary function decline (>−3%/year FEV1 over the ensuing 5 years). Illumina MiSeq paired-end sequencing of the V3-V4 region of the 16S rRNA was used to define the airway microbiome.
Results Based on the primary outcome analysed, 17 individuals (16%) subsequently progressed to eESLD. They were more likely to have sputum with low alpha diversity, dominated by specific pathogens including Pseudomonas. Communities with abundant Streptococcus were observed to be protective. Microbial communities clustered together by baseline lung disease stage and subsequent progression to eESLD. Multivariable analysis identified baseline lung function and alpha diversity as independent predictors of eESLD. For the secondary outcomes, 58 and 47 patients were classified as rapid progressors based on absolute and relative definitions of lung function decline, respectively. Patients with low alpha diversity were similarly more likely to be classified as experiencing rapid lung function decline over the ensuing 5 years when adjusted for baseline lung function.
Conclusions We observed that the diversity of microbial communities in CF airways is predictive of progression to eESLD and disproportionate lung function decline and may therefore represent a novel biomarker.
- cystic fibrosis
- respiratory infection
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Contributors NA was primarily responsible for sputum sample collection, extraction and microbiome analysis. Sample analysis and statistical analyses were performed by NA, AH, MGS, MLW, CDS and RS. NA, HRR, CDS and MDP were responsible for collection and maintenance of the CACFC Biobank and clinical care records, and documentation. NA was responsible for the creation of the initial draft of the manuscript. All authors contributed to development of the final manuscript. MDP is the guarantor of this work.
Funding This study was supported by a grant from the Canadian Institute of Health Research to MDP, grant number 364568.
Competing interests MDP, HRR and MGS have received research funding from Gilead Sciences. MDP and HRR have participated in advisory boards and/or performed consulting work for Vertex but both declined honoraria. NA, AH, RS, MLW and CDS have no conflicts to declare.
Patient consent Not required.
Ethics approval Conjoint Health Research Ethics Board of the University of Calgary (REB-15-2744).
Provenance and peer review Not commissioned; externally peer reviewed.
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