Changes in Cystic Fibrosis Airway Microbial Community Associated with a Severe Decline in Lung Function

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.

Airway microbiota across age and disease spectrum in cystic fibrosis

“…We specifically examined taxa reported in prior CF microbiota and expanded culture analyses [40–42]. Rothia was detected with median relative abundance of 0.15%, ranging from 0.97% in those aged <2 years to 0% in those aged ⩾18 years.…”

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

“…However, with the onset of clinical exacerbations, a decrease in the dominant taxa was observed in some patients (Carmody et al, 2015). The advent of high-throughput detection methods to profile CF microbiota can facilitate the rapid identification of colonizing organisms and detect changes in microbial diversity as disease progresses (Flight et al, 2015), and molecular signatures of species associated with different levels lung function may have potential as predictive biomarkers for clinical deterioration in CF (Paganin et al, 2015). The emerging data on changes in the bacterial community of the CF lung are the subject of a recent review by Caverly et al (2015).…”

Lentiviral-mediated phenotypic correction of cystic fibrosis pigs

“…We also observed an increase in CFTR mRNA levels in treated tissues. Loss of CFTR function leads to the development of chronic bacterial lung infections (26, 27). In CF pigs, loss of CFTR-mediated bicarbonate transport leads to acidic airways and impaired bacterial killing (16).…”