Changes in cystic fibrosis airway microbial community associated with a severe decline in lung function

PLoS One. 2015 Apr 21;10(4):e0124348. doi: 10.1371/journal.pone.0124348. eCollection 2015.

Abstract

Cystic fibrosis (CF) is a genetic disease resulting in chronic polymicrobial infections of the airways and progressive decline in lung function. To gain insight into the underlying causes of severe lung diseases, we aimed at comparing the airway microbiota detected in sputum of CF patients with stable lung function (S) versus those with a substantial decline in lung function (SD). Microbiota composition was investigated by using culture-based and culture-independent methods, and by performing multivariate and statistical analyses. Culture-based methods identified some microbial species associated with a worse lung function, i.e. Pseudomonas aeruginosa, Rothia mucilaginosa, Streptococcus pneumoniae and Candida albicans, but only the presence of S. pneumoniae and R. mucilaginosa was found to be associated with increased severe decline in forced expiratory volume in 1 second (FEV1). Terminal-Restriction Fragment Length Polymorphism (T-RFLP) analysis revealed a higher bacterial diversity than that detected by culture-based methods. Molecular signatures with a statistically significant odds ratio for SD status were detected, and classified as Pseudomonas, Burkholderia and Shewanella, while for other Terminal Restriction Fragments (T-RFs) no species assignation was achieved. The analysis of T-RFLP data using ecological biodiversity indices showed reduced Evenness in SD patients compared to S ones, suggesting an impaired ecology of the bacterial community in SD patients. Statistically significant differences of the ecological biodiversity indices among the three sub-groups of FEV1 (normal/mild vs moderate vs severe) were also found, suggesting that the patients with moderate lung disease experienced changes in the airway assembly of taxa. Overall, changes in CF airway microbial community associated with a severe lung function decline were detected, allowing us to define some discriminatory species as well as some discriminatory T-RFs that represent good candidates for the development of predictive biomarkers of substantial decline in lung function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Burkholderia / genetics
  • Burkholderia / isolation & purification
  • Candida albicans / genetics
  • Candida albicans / isolation & purification
  • Cystic Fibrosis / microbiology*
  • Cystic Fibrosis / physiopathology
  • Disease Progression
  • Female
  • Forced Expiratory Volume
  • Humans
  • Lung / microbiology*
  • Lung / physiopathology
  • Male
  • Microbiota
  • Molecular Typing
  • Polymorphism, Restriction Fragment Length
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / isolation & purification
  • Shewanella / genetics
  • Shewanella / isolation & purification
  • Sputum / microbiology
  • Streptococcus pneumoniae / genetics
  • Streptococcus pneumoniae / isolation & purification
  • Young Adult

Grants and funding

This research was supported by grants from the Italian Cystic Fibrosis Research Foundation (FCC) (http://www.fibrosicisticaricerca.it/) to AB [Project FFC #8/2012 (with the contribution of “Delegazione FFC di Latina”, “Delegazione FFC di Imola”, “Delegazione FFC di Cecina”, Associazione Trentina FC onlus in ricordo di Vanessa Weber, and “Associazione Davide e Guido – Insieme – Fibrosi Cistica Trust Online) and Project FFC #10/2014 (with the contribution of “Delegazione FFC di Villa D'Almè – Bergamo”, “Gruppo di Sostegno FFC di Reggello Firenze”, Gruppo di Sostegno FFC di Lainate”, and “Delegazione FFC di Verbania e V.C.O”)]. PP, VT, and MC were supported by grants awarded by the Italian Cystic Fibrosis Research Foundation. The funders had no role in study design, data collection, analysis and interpretation of the data, decision to publish, or preparation of the manuscript.