Lung function and microbiota diversity in cystic fibrosis

Leah Cuthbertson, Alan W Walker, Anna E Oliver, Geraint B Rogers, Damian W Rivett, Thomas H Hampton, Alix Ashare, Stuart Elborn, Anthony De Soyza, Mary Carroll, Lucas R Hoffman, Clare Lanyon, Samuel Moskowitz, George O'Toole, Julian Parkhill, Paul J Planet, Charlotte Teneback, Michael Tunney, Jonathan Zuckerman, Kenneth D BruceChris van der Gast* (Corresponding Author)

*Corresponding author for this work

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Chronic infection and concomitant airway inflammation is the leading cause of morbidity and mortality for people living with cystic fibrosis (CF). Although chronic infection in CF is undeniably polymicrobial, involving a lung microbiota, infection surveillance and control approaches remain underpinned by classical aerobic culture-based microbiology. How to use microbiomics to direct clinical management of CF airway infections remains a crucial challenge. A pivotal step towards leveraging microbiome approaches in CF clinical care is to understand the ecology of the CF lung microbiome and identify ecological patterns of CF microbiota across a wide spectrum of lung disease. Assessing sputum samples from 299 patients attending 13 CF centres in Europe and the USA, we determined whether the emerging relationship of decreasing microbiota diversity with worsening lung function could be considered a generalised pattern of CF lung microbiota and explored its potential as an informative indicator of lung disease state in CF.

We tested and found decreasing microbiota diversity with a reduction in lung function to be a significant ecological pattern. Moreover, the loss of diversity was accompanied by an increase in microbiota dominance. Subsequently, we stratified patients into lung disease categories of increasing disease severity to further investigate relationships between microbiota characteristics and lung function, and the factors contributing to microbiota variance. Core taxa group composition became highly conserved within the severe disease category, while the rarer satellite taxa underpinned the high variability observed in the microbiota diversity. Further, the lung microbiota of individual patient were increasingly dominated by recognised CF pathogens as lung function decreased. Conversely, other bacteria, especially obligate anaerobes, increasingly dominated in those with better lung function. Ordination analyses revealed lung function and antibiotics to be main explanators of compositional variance in the microbiota and the core and satellite taxa. Biogeography was found to influence acquisition of the rarer satellite taxa.

Our findings demonstrate that microbiota diversity and dominance, as well as the identity of the dominant bacterial species, in combination with measures of lung function, can be used as informative indicators of disease state in CF.
Original languageEnglish
Article number45
Number of pages13
Publication statusPublished - 2 Apr 2020

Bibliographical note

We thank the patients and staff at each of the contributing centres for their involvement, time and patience in sample collection. This study was supported by grants from the UK Natural Environment Research Council (NE/H019456/1) and the Wellcome Trust (WT 098051). AWW receives core funding support from the Scottish Government’s Rural and Environment Science and Analytical Services (RESAS) division. AA and GO received support from the Dartmouth Translational Research Core (CFF RDP STANTO15R0) for acquiring samples.


  • Antibiotics
  • Biogeography
  • Cystic fibrosis
  • Disease severity
  • Ecological patterns
  • Lung function
  • Lung microbiome
  • Lung microbiota
  • Microbial surveillance
  • AGE


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