The Adult Cystic Fibrosis Airway Microbiota Is Stable over Time and Infection Type, and Highly Resilient to Antibiotic Treatment of Exacerbations

Abstract

Cystic fibrosis (CF) is characterized by defective mucociliary clearance and chronic airway infection by a complex microbiota. Infection, persistent inflammation and periodic episodes of acute pulmonary exacerbation contribute to an irreversible decline in CF lung function. While the factors leading to acute exacerbations are poorly understood, antibiotic treatment can temporarily resolve pulmonary symptoms and partially restore lung function. Previous studies indicated that exacerbations may be associated with changes in microbial densities and the acquisition of new microbial species. Given the complexity of the CF microbiota, we applied massively parallel pyrosequencing to identify changes in airway microbial community structure in 23 adult CF patients during acute pulmonary exacerbation, after antibiotic treatment and during periods of stable disease. Over 350,000 sequences were generated, representing nearly 170 distinct microbial taxa. Approximately 60% of sequences obtained were from the recognized CF pathogens Pseudomonas and Burkholderia, which were detected in largely non-overlapping patient subsets. In contrast, other taxa including Prevotella, Streptococcus, Rothia and Veillonella were abundant in nearly all patient samples. Although antibiotic treatment was associated with a small decrease in species richness, there was minimal change in overall microbial community structure. Furthermore, microbial community composition was highly similar in patients during an exacerbation and when clinically stable, suggesting that exacerbations may represent intrapulmonary spread of infection rather than a change in microbial community composition. Mouthwash samples, obtained from a subset of patients, showed a nearly identical distribution of taxa as expectorated sputum, indicating that aspiration may contribute to colonization of the lower airways. Finally, we observed a strong correlation between low species richness and poor lung function. Taken together, these results indicate that the adult CF lung microbiome is largely stable through periods of exacerbation and antibiotic treatment and that short-term compositional changes in the airway microbiota do not account for CF pulmonary exacerbations.

Antibiotic Management of Lung Infections in Cystic Fibrosis. I. The Microbiome, Methicillin-Resistant Staphylococcus aureus, Gram-Negative Bacteria, and Multiple Infections

“…The Human Microbiome Project, a National Institutes of Health-sponsored initiative launched in 2007, applying culture-independent methods to assess bacterial ecology, has significantly broadened this view. Numerous studies now provide compelling evidence that the airways of persons with CF may be inhabited by diverse bacterial communities composed of dozens of species (14)(15)(16)(17)(18)(19)(20)(21)(22)(23). In addition to "typical" CF pathogens, "nonpathogenic oral bacteria," including many obligate and facultative anaerobic species, are often present in densities that well exceed those of the traditional opportunists associated with CF (4).…”

“…Fodor and colleagues (15) showed that bacterial community richness decreased transiently with antibiotic therapy but rebounded quickly thereafter. Zhao and colleagues (23) similarly showed a significant decrease in diversity with antibiotic therapy of exacerbation but did not find significant changes in diversity when comparing samples from periods of clinical stability to those taken at the onset of exacerbation symptoms, a finding that was subsequently confirmed in a larger study (28).…”

“…Conventional bacterial culture in aerobic conditions allows isolation of a limited number of organisms. Extended culture methods identify a much wider range of bacteria, which include more difficult to culture bacteria, such as anaerobic bacteria (4,15,23). At present, there is no readily available methodology to identify all of these organisms in a way that makes this information valuable for clinical treatment (77).…”

A Brave New World: The Lung Microbiota in an Era of Change

“…In cystic fibrosis, changes in bacterial diversity are associated with disease progression and consequent colonization with pathogens (22). Diversity of airway microbiota in cystic fibrosis has been found to decrease significantly with disease stage (22,23). Also, the composition of the airway microbiota before an exacerbation event may be relevant to determine the microbial constituents involved in the exacerbations (24).…”

Le microbiome pulmonaire en 2015

“…À côté de P. aeruginosa, d'autres espèces ou genres (Streptococcus, Prevotella, Veillonella, Rothia, Actinomyces, Gemella, Granulicatella, Fusobacterium, Neisseria, Atopobium, etc.) ont été identifiés comme étant importants dans la constitution du microbiote pulmonaire au cours de la mucoviscidose [9,11,[13][14][15][16][17][18][19][20]. L'ensemble de ces études tend à montrer qu'il existe une corrélation significative entre la diversité du microbiome pulmonaire et l'âge, le statut clinique et l'état de la fonction pulmonaire des patients [11, 15-17, 20, 26].…”