Airway Microbiota and Pathogen Abundance in Age-Stratified Cystic Fibrosis Patients

Abstract

Bacterial communities in the airways of cystic fibrosis (CF) patients are, as in other ecological niches, influenced by autogenic and allogenic factors. However, our understanding of microbial colonization in younger versus older CF airways and the association with pulmonary function is rudimentary at best. Using a phylogenetic microarray, we examine the airway microbiota in age stratified CF patients ranging from neonates (9 months) to adults (72 years). From a cohort of clinically stable patients, we demonstrate that older CF patients who exhibit poorer pulmonary function possess more uneven, phylogenetically-clustered airway communities, compared to younger patients. Using longitudinal samples collected form a subset of these patients a pattern of initial bacterial community diversification was observed in younger patients compared with a progressive loss of diversity over time in older patients. We describe in detail the distinct bacterial community profiles associated with young and old CF patients with a particular focus on the differences between respective “early” and “late” colonizing organisms. Finally we assess the influence of Cystic Fibrosis Transmembrane Regulator (CFTR) mutation on bacterial abundance and identify genotype-specific communities involving members of the Pseudomonadaceae, Xanthomonadaceae, Moraxellaceae and Enterobacteriaceae amongst others. Data presented here provides insights into the CF airway microbiota, including initial diversification events in younger patients and establishment of specialized communities of pathogens associated with poor pulmonary function in older patient populations.

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

“…In contrast, several cross-sectional and longitudinal studies of adults have shown that diversity decreases with age and declining lung function (14,18,22,23). Analyses of respiratory specimens from persons with end-stage lung disease or from lung explants show very constrained communities, often limited to a single dominant species (23,27).…”

“…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).…”

“…Limited studies of children with CF indicate that bacterial community diversity (a measure of both the number and relative abundances of the species present) increases with age (14,26). In contrast, several cross-sectional and longitudinal studies of adults have shown that diversity decreases with age and declining lung function (14,18,22,23).…”

Spatial distribution of microbial communities in the cystic fibrosis lung

“…Most mortality in CF is due to microbial infections of the lungs, which lead to eventual respiratory failure (Cystic Fibrosis Foundation, 2008). Pseudomonas aeruginosa, Staphylococcus aureus and Burkholderia cepacia are common pathogens cultured from adult CF patients, but recent studies have demonstrated that microbial communities in the CF airways are highly diverse (Armougom et al, 2009;Rogers et al, 2009;Cox et al, 2010;Guss et al, 2011). Culture-based analysis of bronchoalveolar lavage (BAL) and autopsy samples indicates that microbial populations vary significantly in different spatial regions of the CF lung (Smith et al, 1998;Gutierrez et al, 2001;Gilchrist et al, 2011).…”

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].…”