Airway microbiota across age and disease spectrum in cystic fibrosis

Our objectives were to characterise the microbiota in cystic fibrosis (CF) bronchoalveolar lavage fluid (BALF), and determine its relationship to inflammation and disease status. BALF from paediatric and adult CF patients and paediatric disease controls undergoing clinically indicated bronchoscopy was analysed for total bacterial load and for microbiota by 16S rDNA sequencing. We examined 191 BALF samples (146 CF and 45 disease controls) from 13 CF centres. In CF patients aged <2 years, nontraditional taxa (e.g. Streptococcus, Prevotella and Veillonella) constituted ∼50% of the microbiota, whereas in CF patients aged ≥6 years, traditional CF taxa (e.g. Pseudomonas, Staphylococcus and Stenotrophomonas) predominated. Sequencing detected a dominant taxon not traditionally associated with CF (e.g. Streptococcus or Prevotella) in 20% of CF BALF and identified bacteria in 24% of culture-negative BALF. Microbial diversity and relative abundance of Streptococcus, Prevotella and Veillonella were inversely associated with airway inflammation. Microbiota communities were distinct in CF compared with disease controls, but did not differ based on pulmonary exacerbation status in CF. The CF microbiota detected in BALF differs with age. In CF patients aged <2 years, Streptococcus predominates, whereas classic CF pathogens predominate in most older children and adults. Bacterial taxa detected in cystic fibrosis bronchoalveolar lavage fluid differ by age and inflammatory response http://ow.ly/2uV230eFA0W

[1]  D. Frank,et al.  Investigation of sinonasal microbiome spatial organization in chronic rhinosinusitis , 2017, International forum of allergy & rhinology.

[2]  C. Robertson,et al.  Airway Microbiota in Bronchoalveolar Lavage Fluid from Clinically Well Infants with Cystic Fibrosis , 2016, PloS one.

[3]  L. Raskin,et al.  Culture-Independent Identification of Nontuberculous Mycobacteria in Cystic Fibrosis Respiratory Samples , 2016, PloS one.

[4]  Emily A. Knapp,et al.  Changing Epidemiology of the Respiratory Bacteriology of Patients With Cystic Fibrosis. , 2016, Chest.

[5]  J. Harris,et al.  Molecular Identification of Staphylococcus aureus in Airway Samples from Children with Cystic Fibrosis , 2016, PloS one.

[6]  N. Pace,et al.  Microbial aerosol liberation from soiled textiles isolated during routine residuals handling in a modern health care setting , 2015, Microbiome.

[7]  Emily S. Charlson,et al.  Multicenter Comparison of Lung and Oral Microbiomes of HIV-infected and HIV-uninfected Individuals. , 2015, American journal of respiratory and critical care medicine.

[8]  S. Donaldson,et al.  Lung microbiota across age and disease stage in cystic fibrosis , 2015, Scientific Reports.

[9]  V. Lucidi,et al.  Changes in Cystic Fibrosis Airway Microbial Community Associated with a Severe Decline in Lung Function , 2015, PloS one.

[10]  J. Harris,et al.  Assessment of airway microbiota and inflammation in cystic fibrosis using multiple sampling methods. , 2015, Annals of the American Thoracic Society.

[11]  M. Rosenfeld,et al.  Cystic Fibrosis Foundation pulmonary guideline. pharmacologic approaches to prevention and eradication of initial Pseudomonas aeruginosa infection. , 2014, Annals of the American Thoracic Society.

[12]  T. DeSantis,et al.  The Microbial Community of the Cystic Fibrosis Airway Is Disrupted in Early Life , 2014, PloS one.

[13]  Elissa Murphy,et al.  The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis. , 2014, American journal of respiratory and critical care medicine.

[14]  J. Carlin,et al.  Costs of bronchoalveolar lavage-directed therapy in the first 5 years of life for children with cystic fibrosis. , 2014, The Journal of pediatrics.

[15]  Rohan S. Kulkarni,et al.  Correction: Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation , 2014, Microbiome.

[16]  Barbara A. Bailey,et al.  The upper respiratory tract as a microbial source for pulmonary infections in cystic fibrosis. Parallels from island biogeography. , 2014, American journal of respiratory and critical care medicine.

[17]  Daniel N. Frank,et al.  Explicet: graphical user interface software for metadata-driven management, analysis and visualization of microbiome data , 2013, Bioinform..

[18]  Rohan S. Kulkarni,et al.  Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation , 2013, Microbiome.

[19]  J. Petrosino,et al.  Changes in cystic fibrosis airway microbiota at pulmonary exacerbation. , 2013, Annals of the American Thoracic Society.

[20]  Emily S. Charlson,et al.  Widespread colonization of the lung by Tropheryma whipplei in HIV infection. , 2013, American journal of respiratory and critical care medicine.

[21]  Patrick D Schloss,et al.  Comparison of the respiratory microbiome in healthy nonsmokers and smokers. , 2013, American journal of respiratory and critical care medicine.

[22]  J. Harris,et al.  Inflammation and Airway Microbiota during Cystic Fibrosis Pulmonary Exacerbations , 2013, PloS one.

[23]  Leah M. Feazel,et al.  Sex Differences in the Gut Microbiome Drive Hormone-Dependent Regulation of Autoimmunity , 2013, Science.

[24]  H. Weon,et al.  Effects of PCR cycle number and DNA polymerase type on the 16S rRNA gene pyrosequencing analysis of bacterial communities , 2012, Journal of Microbiology.

[25]  Pelin Yilmaz,et al.  The SILVA ribosomal RNA gene database project: improved data processing and web-based tools , 2012, Nucleic Acids Res..

[26]  D. Frank,et al.  Prevention of Virus-Induced Type 1 Diabetes with Antibiotic Therapy , 2012, The Journal of Immunology.

[27]  S. Dowd,et al.  Direct sampling of cystic fibrosis lungs indicates that DNA-based analyses of upper-airway specimens can misrepresent lung microbiota , 2012, Proceedings of the National Academy of Sciences.

[28]  L. Hoffman,et al.  Long-term cultivation-independent microbial diversity analysis demonstrates that bacterial communities infecting the adult cystic fibrosis lung show stability and resilience , 2012, Thorax.

[29]  Elmar Pruesse,et al.  SINA: Accurate high-throughput multiple sequence alignment of ribosomal RNA genes , 2012, Bioinform..

[30]  Susan Murray,et al.  Decade-long bacterial community dynamics in cystic fibrosis airways , 2012, Proceedings of the National Academy of Sciences.

[31]  Steven L Salzberg,et al.  Fast gapped-read alignment with Bowtie 2 , 2012, Nature Methods.

[32]  P. Sly,et al.  Inflammatory responses to individual microorganisms in the lungs of children with cystic fibrosis. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[33]  M. Surette,et al.  Culture Enriched Molecular Profiling of the Cystic Fibrosis Airway Microbiome , 2011, PloS one.

[34]  J. Carlin,et al.  Effect of bronchoalveolar lavage-directed therapy on Pseudomonas aeruginosa infection and structural lung injury in children with cystic fibrosis: a randomized trial. , 2011, JAMA.

[35]  Rob Knight,et al.  UCHIME improves sensitivity and speed of chimera detection , 2011, Bioinform..

[36]  Patrick D. Schloss,et al.  Assessing and Improving Methods Used in Operational Taxonomic Unit-Based Approaches for 16S rRNA Gene Sequence Analysis , 2011, Applied and Environmental Microbiology.

[37]  J. Curtis,et al.  Analysis of the Lung Microbiome in the “Healthy” Smoker and in COPD , 2011, PloS one.

[38]  M. Wolfgang,et al.  Analysis of the Bacterial Communities Present in Lungs of Patients with Cystic Fibrosis from American and British Centers , 2010, Journal of Clinical Microbiology.

[39]  G. Bellon,et al.  Relative contribution of Prevotella intermedia and Pseudomonas aeruginosa to lung pathology in airways of patients with cystic fibrosis , 2010, Thorax.

[40]  M. Surette,et al.  The genus Prevotella in cystic fibrosis airways. , 2010, Anaerobe.

[41]  Eoin L. Brodie,et al.  Airway Microbiota and Pathogen Abundance in Age-Stratified Cystic Fibrosis Patients , 2010, PloS one.

[42]  Lior Pachter,et al.  Disordered Microbial Communities in Asthmatic Airways , 2010, PloS one.

[43]  L. Saiman,et al.  Respiratory microbiology of patients with cystic fibrosis in the United States, 1995 to 2005. , 2009, Chest.

[44]  G. Döring,et al.  Antibiotic-resistant obligate anaerobes during exacerbations of cystic fibrosis patients. , 2009, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[45]  P. Harris,et al.  Research electronic data capture (REDCap) - A metadata-driven methodology and workflow process for providing translational research informatics support , 2009, J. Biomed. Informatics.

[46]  J. Emerson,et al.  Impact of Pseudomonas and Staphylococcus infection on inflammation and clinical status in young children with cystic fibrosis. , 2009, The Journal of pediatrics.

[47]  J. Sarles,et al.  Molecular Detection of Multiple Emerging Pathogens in Sputa from Cystic Fibrosis Patients , 2008, PloS one.

[48]  M. Wolfgang,et al.  Detection of anaerobic bacteria in high numbers in sputum from patients with cystic fibrosis. , 2008, American journal of respiratory and critical care medicine.

[49]  N. Pace,et al.  Molecular identification of bacteria in bronchoalveolar lavage fluid from children with cystic fibrosis , 2007, Proceedings of the National Academy of Sciences.

[50]  M. Surette,et al.  Cystic fibrosis: a polymicrobial infectious disease. , 2006, Future microbiology.

[51]  G. Rogers,et al.  Characterization of Bacterial Community Diversity in Cystic Fibrosis Lung Infections by Use of 16S Ribosomal DNA Terminal Restriction Fragment Length Polymorphism Profiling , 2004, Journal of Clinical Microbiology.

[52]  R. Gibson,et al.  Pathophysiology and management of pulmonary infections in cystic fibrosis. , 2003, American journal of respiratory and critical care medicine.

[53]  J. Emerson,et al.  Defining a pulmonary exacerbation in cystic fibrosis. , 2001, The Journal of pediatrics.

[54]  J. Emerson,et al.  Microbiology of sputum from patients at cystic fibrosis centers in the United States. , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[55]  P Green,et al.  Base-calling of automated sequencer traces using phred. II. Error probabilities. , 1998, Genome research.

[56]  P. Green,et al.  Base-calling of automated sequencer traces using phred. I. Accuracy assessment. , 1998, Genome research.

[57]  C. Wainwright,et al.  Bronchoscopy-guided antimicrobial therapy for cystic fibrosis. , 2013, The Cochrane database of systematic reviews.

[58]  Neil Hunter,et al.  Determination of bacterial load by real-time PCR using a broad-range (universal) probe and primers set. , 2002, Microbiology.