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.
Highlights
Cystic fibrosis (CF) is the most frequent autosomal recessive life-threatening disease affecting 70,000 individuals worldwide, resulting in a progressive lung function decline
(n = 38) 17 male 21 female including CFTR genotype, gender, age, forced expiratory volume in 1 second (FEV1)%, Body Mass Index (BMI), and nebulised antibiotics or oral azithromycin treatment are provided in S1 and S2 Tables
No significant differences were found for FEV1 (I) vs FEV1 (III). We used both culture-dependent methods for detection of aerobic and anaerobic bacteria and fungi, and a culture-independent method by terminal restriction fragment length polymorphism (T-RFLP), which provide a fingerprint of the most highly abundant members of the community
Summary
Cystic fibrosis (CF) is the most frequent autosomal recessive life-threatening disease affecting 70,000 individuals worldwide, resulting in a progressive lung function decline. The percentage of predicted forced expiratory volume in 1 s (FEV1%) is commonly used to monitor lung function in CF and represents the best available predictor of survival for patients with CF [1], [2]. Several studies have evidenced that some CF patients’ FEV1 seriously decline despite antibiotic treatment [4] and that both long- and short-term fluctuations in lung function can be related to disease severity due to CFTR gene mutations, chronic bacterial infection, and periodic pulmonary exacerbation [3]. Interpreting the significance of changes in FEV1% over time first requires a more in-depth comprehension of the airway microbial community composition [6]
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