Composition Of Airway Microbiota Research Articles

41 Taxonomic signatures of CF airway microbiota distinguish between patients with lower and higher pulmonary function decline

Objective To gain insight into the underlying causes of severe lung diseases, we compared the airway microbiota detected in sputum of CF patients with stable lung function (S) versus those with a substantial decline in lung function (SD). Methods Fifty-two patients belonging to three FEV1 groups (normal/mild, FEV1 >70%; moderate, 40 Results A sharp difference in the structure and composition of airway microbiota between S and SD patients was found, especially in patients with severe lung disease, where Pseudomonas represented the most abundant genus. A cooccurrence network analysis showed that microbial communities were less complex in SD patients than in S ones. Moreover, an inverse relationship between bacterial community diversity and disease severity was found. Indeed, the analysis of the main biodiversity indices on microbiota data has shown a significant drop passing from normal/mild FEV1 group to moderate lung disease FEV1 group suggesting that the patients with intermediate FEV1 values are experiencing changes in the airway assembly of taxa. Conclusion We can claim that bacterial lung microbiota is modified along with substantial decline in lung function. Higher levels of pulmonary deficiency can lead to a drastic decrement of bacterial community complexity leaving the way clear for the proliferation of opportunistic pathogens. Grants FFC #8/2012 and FFC #10/2014.

Matrix metalloproteinases vary with airway microbiota composition and lung function in non-cystic fibrosis bronchiectasis.

Despite growing evidence for the roles of airway remodeling and bacterial infection in the progression of non-cystic fibrosis bronchiectasis, relationships between collagen-degrading proteases and chronic airway infection are poorly understood. The aim of this study was to determine which matrix metalloproteinases (MMPs) are elevated in bronchiectasis, whether these MMP levels vary based on patients' dominant infective microbe, and how these levels correlate with clinical measures of disease severity. We determined concentrations of nine MMPs and four tissue inhibitors of metalloproteinases (TIMPs) in induced sputum from 86 patients with bronchiectasis and 8 healthy control subjects by Luminex protein assay. Concentrations were then assessed in relation to lung function, inflammatory markers, and airway microbiota composition, determined by 16S rRNA gene amplicon sequencing. Airway microbiota composition was classified as Pseudomonas aeruginosa-dominated, Haemophilus influenzae-dominated, or dominated by another species. MMP-8 and MMP-9 activity levels were also measured in a subset of patients. MMP-1, -3, -7, -8, and -9 and TIMP-2 and -4 levels, as well as MMP-8/TIMP-1 and MMP-9/TIMP-1 ratios, were significantly higher in patients with bronchiectasis than in healthy control subjects (all: P < 0.001, except MMP-7: P < 0.05). Patients with bronchiectasis with H. influenzae-dominated airway infections demonstrated higher MMP-2 levels (P < 0.01) and MMP-8 activity (P < 0.05) than those with P. aeruginosa-dominated airway infections. Among patients with bronchiectasis, there were significant inverse correlations between FEV1 as a percentage of predicted value, MMP-8 and MMP-1 levels, and MMP-8/TIMP-1 and MMP-9/TIMP-1 ratios (P < 0.01). Increased MMP levels (particularly MMP-8 and MMP-1) and MMP/TIMP ratios in patients with bronchiectasis compared with healthy control subjects correlated with lower lung function and higher levels of inflammatory markers. Further, MMP profiles differed in patients with bronchiectasis according to the dominant pathogen determined by gene sequencing, raising the possibility of differential airway remodeling according to airway microbiology.

Impact of the CFTR-potentiator ivacaftor on airway microbiota in cystic fibrosis patients carrying a G551D mutation.

BackgroundAirway microbiota composition has been clearly correlated with many pulmonary diseases, and notably with cystic fibrosis (CF), an autosomal genetic disorder caused by mutation in the CF transmembrane conductance regulator (CFTR). Recently, a new molecule, ivacaftor, has been shown to re-establish the functionality of the G551D-mutated CFTR, allowing significant improvement in lung function.Objective and MethodsThe purpose of this study was to follow the evolution of the airway microbiota in CF patients treated with ivacaftor, using quantitative PCR and pyrosequencing of 16S rRNA amplicons, in order to identify quantitative and qualitative changes in bacterial communities. Three G551D children were followed up longitudinally over a mean period of more than one year covering several months before and after initiation of ivacaftor treatment.Results129 operational taxonomy units (OTUs), representing 64 genera, were identified. There was no significant difference in total bacterial load before and after treatment. Comparison of global community composition found no significant changes in microbiota. Two OTUs, however, showed contrasting dynamics: after initiation of ivacaftor, the relative abundance of the anaerobe Porphyromonas 1 increased (p<0.01) and that of Streptococcus 1 (S. mitis group) decreased (p<0.05), possibly in relation to the anti-Gram-positive properties of ivacaftor. The anaerobe Prevotella 2 correlated positively with the pulmonary function test FEV-1 (r=0.73, p<0.05). The study confirmed the presumed positive role of anaerobes in lung function.ConclusionSeveral airway microbiota components, notably anaerobes (obligate or facultative anaerobes), could be valuable biomarkers of lung function improvement under ivacaftor, and could shed light on the pathophysiology of lung disease in CF patients.

A Novel Microbiota Stratification System Predicts Future Exacerbations in Bronchiectasis

Although airway microbiota composition correlates with clinical measures in non-cystic fibrosis bronchiectasis, these data are unlikely to provide useful prognostic information at the individual patient level. A system enabling microbiota data to be applied clinically would represent a substantial translational advance. This study aims to determine whether stratification of patients according to the predominant microbiota taxon can provide improved clinical insight compared with standard diagnostics. The presence of bacterial respiratory pathogens was assessed in induced sputum from 107 adult patients by culture, quantitative PCR, and, in 96 samples, by ribosomal gene pyrosequencing. Prospective analysis was performed on samples from 42 of these patients. Microbiological data were correlated with concurrent clinical measures and subsequent outcomes. Microbiota analysis defined three groups: Pseudomonas aeruginosa dominated (n = 26), Haemophilus influenzae dominated (n = 34), and other taxa dominated (n = 36). Patients with P. aeruginosa- and H. influenzae-dominated communities had significantly worse lung function, higher serum levels of C-reactive protein (CRP), and higher sputum levels of IL-8 and IL-1β. Predominance of P. aeruginosa, followed by Veillonella species, was the best predictor of future exacerbation frequency, with H. influenzae-dominated communities having significantly fewer episodes. Detection of P. aeruginosa was associated with poor lung function and exacerbation frequency, irrespective of analytical strategy. Quantitative PCR revealed significant correlations between H. influenzae levels and sputum IL-8, IL-1β, and serum CRP. Genus richness was negatively correlated with 24-hour sputum weight, age, serum CRP, sputum IL-1β, and IL-8. Stratification of patients with non-cystic fibrosis bronchiectasis on the basis of predominant bacterial taxa is more clinically informative than either conventional culture or quantitative PCR-based analysis. Further investigation is now required to assess the mechanistic basis of these associations.

Microbial communities in the respiratory tract of patients with interstitial lung disease

BackgroundMolecular methods based on phylogenetic differences in the 16S rRNA gene are able to characterise the microbiota of the respiratory tract in health and disease.ObjectivesOur goals were (1) to characterise...

100 Comparison of airway microbiota composition in healthy children and children with CF

Introduction and Aims: Although a number of studies have characterized airway microbiota composition in healthy and CF adult populations, limited data is available for the paediatric population. The aim of this study was to define, using culture based methods, the composition of the airway microbiota in age-matched healthy and CF paediatric groups. Methods: Induced sputum samples (CF) and cough swabs (CF, age-matched healthy volunteers) were collected and processed using both aerobic and strict anaerobic bacteriological culture techniques. Bacteria within the samples were detected by plating on selective agars and identified by PCR and sequencing of 16S ribosomal RNA genes. Results: Samples were collected from 21 healthy volunteers (mean (SD) age 11.0 (3.5) yrs; 13M:8F) and from 12 children with CF (mean (SD) age 12.8 (3.2) yrs; 6M:6F) when clinically stable. Bacteria were detected in all samples from CF patients and in 18/21 (86%) healthy volunteers. Aerobic bacteria from genera including Streptococcus, Staphylococcus, Pseudomonas and Haemophilus were detected in both cohorts with Pseudomonas [CF, n = 2/12 (17%); control, n = 1/21 (5%)] and Haemophilus [CF, n = 7/12 (58%); control n = 4/21 (19%)] present in a greater number of CF patients compared to controls. Anaerobic bacteria from genera including Prevotella, Veillonella, and Actinomyces were detected in both cohorts. Conclusion: Aerobic and anaerobic bacteria have been detected by culture in the lungs of children with CF and healthy children. Pseudomonas and Haemophilus, recognised as pathogens in CF patients, were more prevalent in CF patients compared to controls. Funded by US-Ireland Project Partnership Grant.

101 Microbial communities and interactions in chronic lung infection in cystic fibrosis patients

Introduction and Aims: Although a number of studies have characterized airway microbiota composition in healthy and CF adult populations, limited data is available for the paediatric population. The aim of this study was to define, using culture based methods, the composition of the airway microbiota in age-matched healthy and CF paediatric groups. Methods: Induced sputum samples (CF) and cough swabs (CF, age-matched healthy volunteers) were collected and processed using both aerobic and strict anaerobic bacteriological culture techniques. Bacteria within the samples were detected by plating on selective agars and identified by PCR and sequencing of 16S ribosomal RNA genes. Results: Samples were collected from 21 healthy volunteers (mean (SD) age 11.0 (3.5) yrs; 13M:8F) and from 12 children with CF (mean (SD) age 12.8 (3.2) yrs; 6M:6F) when clinically stable. Bacteria were detected in all samples from CF patients and in 18/21 (86%) healthy volunteers. Aerobic bacteria from genera including Streptococcus, Staphylococcus, Pseudomonas and Haemophilus were detected in both cohorts with Pseudomonas [CF, n = 2/12 (17%); control, n = 1/21 (5%)] and Haemophilus [CF, n = 7/12 (58%); control n = 4/21 (19%)] present in a greater number of CF patients compared to controls. Anaerobic bacteria from genera including Prevotella, Veillonella, and Actinomyces were detected in both cohorts. Conclusion: Aerobic and anaerobic bacteria have been detected by culture in the lungs of children with CF and healthy children. Pseudomonas and Haemophilus, recognised as pathogens in CF patients, were more prevalent in CF patients compared to controls. Funded by US-Ireland Project Partnership Grant.

Clinical measures of disease in adult non-CF bronchiectasis correlate with airway microbiota composition

RationaleDespite the potentially important roles for infection in adult non-cystic fibrosis (CF) bronchiectasis disease progression, the bacterial species present in the lower airways of these patients is poorly characterised.ObjectivesTo provide...

The emerging relationship between the airway microbiota and chronic respiratory disease: clinical implications

Until recently, relationships between evidence of colonization or infection by specific microbial species and the development, persistence or exacerbation of pulmonary disease have informed our opinions of airway microbiology. However, recent applications of culture-independent tools for microbiome profiling have revealed a more diverse microbiota than previously recognized in the airways of patients with chronic pulmonary disease. New evidence indicates that the composition of airway microbiota differs in states of health and disease and with severity of symptoms and that the microbiota, as a collective entity, may contribute to pathophysiologic processes associated with chronic airway disease. Here, we review the evolution of airway microbiology studies of chronic pulmonary disease, focusing on asthma, chronic obstructive pulmonary disease and cystic fibrosis. Building on evidence derived from traditional microbiological approaches and more recent culture-independent microbiome studies, we discuss the implications of recent findings on potential microbial determinants of respiratory health or disease.

Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma

Improvement in lung function after macrolide antibiotic therapy has been attributed to reduction in bronchial infection by specific bacteria. However, the airway might be populated by a more diverse microbiota, and clinical features of asthma might be associated with characteristics of the airway microbiota present. We sought to determine whether relationships exist between the composition of the airway bacterial microbiota and clinical features of asthma using culture-independent tools capable of detecting the presence and relative abundance of most known bacteria. In this pilot study bronchial epithelial brushings were collected from 65 adults with suboptimally controlled asthma participating in a multicenter study of the effects of clarithromycin on asthma control and 10 healthy control subjects. Acombination of high-density 16S ribosomal RNA microarray and parallel clone library-sequencing analysis was used to profile the microbiota and examine relationships with clinical measurements. Compared with control subjects, 16S ribosomal RNA amplicon concentrations (a proxy for bacterial burden) and bacterial diversity were significantly higher among asthmatic patients. In multivariate analyses airway microbiota composition and diversity were significantly correlated with bronchial hyperresponsiveness. Specifically, the relative abundance of particular phylotypes, including members of the Comamonadaceae, Sphingomonadaceae, Oxalobacteraceae, and other bacterial families were highly correlated with the degree of bronchial hyperresponsiveness. The composition of bronchial airway microbiota is associated with the degree of bronchial hyperresponsiveness among patients with suboptimally controlled asthma. These findings support the need for further functional studies to examine the potential contribution of members of the airway microbiota in asthma pathogenesis.