Influence of lung CT changes in chronic obstructive pulmonary disease (COPD) on the human lung microbiome

Background Changes in microbial community composition in the lung of patients suffering from moderate to severe COPD have been well documented. However, knowledge about specific microbiome structures in the human lung associated with CT defined abnormalities is limited. Methods Bacterial community composition derived from brush samples from lungs of 16 patients suffering from different CT defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene fragment amplicons. Results We could show that bacterial community composition in patients with changes in CT (either airway or emphysema type changes, designated as severe subtypes) was different from community composition in lungs of patients without visible changes in CT as well as from healthy subjects (designated as mild COPD subtype and control group) (PC1, Padj = 0.002). Higher abundance of Prevotella in samples from patients with mild COPD subtype and from controls and of Streptococcus in the severe subtype cases mainly contributed to the separation of bacterial communities of subjects. No significant effects of treatment with inhaled glucocorticoids on bacterial community composition were detected within COPD cases with and without abnormalities in CT in PCoA. Co-occurrence analysis suggests the presence of networks of co-occurring bacteria. Four communities of positively correlated bacteria were revealed. The microbial communities can clearly be distinguished by their associations with the CT defined disease phenotype. Conclusion Our findings indicate that CT detectable structural changes in the lung of COPD patients, which we termed severe subtypes, are associated with alterations in bacterial communities, which may induce further changes in the interaction between microbes and host cells. This might result in a changed interplay with the host immune system.

[1]  James R. Brown,et al.  Lung microbiome dynamics in chronic obstructive pulmonary disease exacerbations , 2019 .

[2]  J. Wedzicha,et al.  Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary , 2017, European Respiratory Journal.

[3]  Joseph M. Campos,et al.  Different next generation sequencing platforms produce different microbial profiles and diversity in cystic fibrosis sputum. , 2016, Journal of microbiological methods.

[4]  J. Wedzicha,et al.  Current Controversies in the Pharmacological Treatment of Chronic Obstructive Pulmonary Disease. , 2016, American journal of respiratory and critical care medicine.

[5]  A. Clooney,et al.  16S rRNA gene sequencing of mock microbial populations- impact of DNA extraction method, primer choice and sequencing platform , 2016, BMC Microbiology.

[6]  I. Gut,et al.  Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography , 2016, European Respiratory Journal.

[7]  Scot E. Dowd,et al.  Inherent bacterial DNA contamination of extraction and sequencing reagents may affect interpretation of microbiota in low bacterial biomass samples , 2016, Gut Pathogens.

[8]  D. Nelson,et al.  Contributions of tropodithietic acid and biofilm formation to the probiotic activity of Phaeobacter inhibens , 2016, BMC Microbiology.

[9]  M. Simionato,et al.  Intraspecies Variability Affects Heterotypic Biofilms of Porphyromonas gingivalis and Prevotella intermedia: Evidences of Strain-Dependence Biofilm Modulation by Physical Contact and by Released Soluble Factors , 2015, PloS one.

[10]  S. Sethi,et al.  Impaired Innate COPD Alveolar Macrophage Responses and Toll-Like Receptor-9 Polymorphisms , 2015, PloS one.

[11]  D. Sin,et al.  Host Response to the Lung Microbiome in Chronic Obstructive Pulmonary Disease. , 2015, American journal of respiratory and critical care medicine.

[12]  J. Curtis,et al.  Spatial Variation in the Healthy Human Lung Microbiome and the Adapted Island Model of Lung Biogeography. , 2015, Annals of the American Thoracic Society.

[13]  R. Tarran,et al.  Airway hydration and COPD , 2015, Cellular and Molecular Life Sciences.

[14]  Edwin K Silverman,et al.  CT-Definable Subtypes of Chronic Obstructive Pulmonary Disease: A Statement of the Fleischner Society. , 2015, Radiology.

[15]  P. Morris,et al.  Deriving accurate microbiota profiles from human samples with low bacterial content through post-sequencing processing of Illumina MiSeq data , 2015, Microbiome.

[16]  Shengying Qin,et al.  Comparative genome analysis of Prevotella intermedia strain isolated from infected root canal reveals features related to pathogenicity and adaptation , 2015, BMC Genomics.

[17]  S. Brix,et al.  Chronic obstructive pulmonary disease and asthma‐associated Proteobacteria, but not commensal Prevotella spp., promote Toll‐like receptor 2‐independent lung inflammation and pathology , 2015, Immunology.

[18]  R. Hegele,et al.  Loss of GD1-positive Lactobacillus correlates with inflammation in human lungs with COPD , 2015, BMJ Open.

[19]  Piotr Gawron,et al.  VizBin - an application for reference-independent visualization and human-augmented binning of metagenomic data , 2015, Microbiome.

[20]  B. Marsland,et al.  Host–microorganism interactions in lung diseases , 2014, Nature Reviews Immunology.

[21]  Paul Turner,et al.  Reagent and laboratory contamination can critically impact sequence-based microbiome analyses , 2014, BMC Biology.

[22]  Jonas Korlach,et al.  Improved performance of the PacBio SMRT technology for 16S rDNA sequencing. , 2014, Journal of microbiological methods.

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

[24]  Douglas E. Brash,et al.  Common Contaminants in Next-Generation Sequencing That Hinder Discovery of Low-Abundance Microbes , 2014, PloS one.

[25]  D. Lynch,et al.  Clinical and computed tomographic predictors of chronic bronchitis in COPD: a cross sectional analysis of the COPDGene study , 2014, Respiratory Research.

[26]  Robert G. Beiko,et al.  A Phylogenomic View of Ecological Specialization in the Lachnospiraceae, a Family of Digestive Tract-Associated Bacteria , 2014, Genome biology and evolution.

[27]  J. Clemente,et al.  Enrichment of Lung Microbiome with Supraglotic Microbes Is Associated with Increased Pulmonary Inflammation , 2014 .

[28]  David A Lynch,et al.  Quantitative Computed Tomography in Chronic Obstructive Pulmonary Disease , 2013, Journal of thoracic imaging.

[29]  F. Kanat,et al.  Phenotyping of chronic obstructive pulmonary disease using the modified Bhalla scoring system for high-resolution computed tomography. , 2013, Canadian respiratory journal.

[30]  Richard E. Isaacson,et al.  The Lung Microbiome in Moderate and Severe Chronic Obstructive Pulmonary Disease , 2012, PloS one.

[31]  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.

[32]  Curtis Huttenhower,et al.  Microbial Co-occurrence Relationships in the Human Microbiome , 2012, PLoS Comput. Biol..

[33]  Levi Waldron,et al.  Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples , 2012, Genome Biology.

[34]  Joel Cooper,et al.  The lung tissue microbiome in chronic obstructive pulmonary disease. , 2012, American journal of respiratory and critical care medicine.

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

[36]  M. Wjst,et al.  The EvA study: aims and strategy , 2012, European Respiratory Journal.

[37]  M. Engel,et al.  Microbial community structure elucidates performance of Glyceria maxima plant microbial fuel cell , 2012, Applied Microbiology and Biotechnology.

[38]  J. Søndergaard,et al.  Divergent Pro-Inflammatory Profile of Human Dendritic Cells in Response to Commensal and Pathogenic Bacteria Associated with the Airway Microbiota , 2012, PloS one.

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

[40]  Asger Dirksen,et al.  Quantitative CT: Associations between Emphysema, Airway Wall Thickness and Body Composition in COPD , 2011, Pulmonary medicine.

[41]  J. Seo,et al.  Responses to inhaled long-acting beta-agonist and corticosteroid according to COPD subtype. , 2010, Respiratory medicine.

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

[43]  Martin Hartmann,et al.  Introducing mothur: Open-Source, Platform-Independent, Community-Supported Software for Describing and Comparing Microbial Communities , 2009, Applied and Environmental Microbiology.

[44]  A. Agustí,et al.  Nontypeable Haemophilus influenzae Clearance by Alveolar Macrophages Is Impaired by Exposure to Cigarette Smoke , 2009, Infection and Immunity.

[45]  Yasutaka Nakano,et al.  Airway wall thickening and emphysema show independent familial aggregation in chronic obstructive pulmonary disease. , 2008, American journal of respiratory and critical care medicine.

[46]  P. Papapanou,et al.  Prevotella bivia can invade human cervix epithelial (HeLa) cells , 2007, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[47]  L. Lanthier,et al.  Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[48]  A. Servin,et al.  Antagonistic activities of lactobacilli and bifidobacteria against microbial pathogens. , 2004, FEMS microbiology reviews.

[49]  K. Schleifer,et al.  ARB: a software environment for sequence data. , 2004, Nucleic acids research.

[50]  C. Neut,et al.  Self inflicted rectal ulcer: hearing is believing , 2003, Gut.

[51]  R. Schleimer Glucocorticoids suppress inflammation but spare innate immune responses in airway epithelium. , 2004, Proceedings of the American Thoracic Society.

[52]  Nikos Kyrpides,et al.  Genome Sequence and Analysis of the Oral Bacterium Fusobacterium nucleatum Strain ATCC 25586 , 2002, Journal of bacteriology.

[53]  M. Röllinghoff,et al.  Induction of TNF in Human Alveolar Macrophages As a Potential Evasion Mechanism of Virulent Mycobacterium tuberculosis1 , 2002, The Journal of Immunology.

[54]  P. Diaz,et al.  Fusobacterium nucleatum supports the growth of Porphyromonas gingivalis in oxygenated and carbon-dioxide-depleted environments. , 2002, Microbiology.

[55]  S. Rennard,et al.  Alternative Mechanisms for Long-Acting β2-Adrenergic Agonists in COPD , 2001 .

[56]  R. Genco,et al.  Interactions between Periodontal Bacteria and Human Oral Epithelial Cells: Fusobacterium nucleatum Adheres to and Invades Epithelial Cells , 2000, Infection and Immunity.

[57]  A. Progulske-Fox,et al.  Invasion of Human Oral Epithelial Cells byPrevotella intermedia , 1998, Infection and Immunity.

[58]  David J. Bradshaw,et al.  Role of Fusobacterium nucleatum and Coaggregation in Anaerobe Survival in Planktonic and Biofilm Oral Microbial Communities during Aeration , 1998, Infection and Immunity.

[59]  K. Schleifer,et al.  Combined Molecular and Conventional Analyses of Nitrifying Bacterium Diversity in Activated Sludge: Nitrosococcus mobilis and Nitrospira-Like Bacteria as Dominant Populations , 1998, Applied and Environmental Microbiology.

[60]  A. Wanner,et al.  Mucociliary clearance in the airways. , 1996, American journal of respiratory and critical care medicine.

[61]  J. Ruiz,et al.  Bacterial infection in chronic obstructive pulmonary disease. A study of stable and exacerbated outpatients using the protected specimen brush. , 1995, American journal of respiratory and critical care medicine.

[62]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[63]  P. Brandtzaeg Humoral immune response patterns of human mucosae: induction and relation to bacterial respiratory tract infections. , 1992, The Journal of infectious diseases.

[64]  D. I. Hay,et al.  Adhesive properties of strains of Fusobacterium nucleatum of the subspecies nucleatum, vincentii and polymorphum. , 1991, Oral microbiology and immunology.

[65]  H. Reynolds,et al.  Macrophages and polymorphonuclear neutrophils in lung defense and injury. , 1990, The American review of respiratory disease.

[66]  L. Moore,et al.  Coaggregation of Fusobacterium nucleatum, Selenomonas flueggei, Selenomonas infelix, Selenomonas noxia, and Selenomonas sputigena with strains from 11 genera of oral bacteria , 1989, Infection and immunity.

[67]  H. Towbin,et al.  Receptor analogs and monoclonal antibodies that inhibit adherence of Bordetella pertussis to human ciliated respiratory epithelial cells , 1988, The Journal of experimental medicine.

[68]  A. Schaffner Therapeutic concentrations of glucocorticoids suppress the antimicrobial activity of human macrophages without impairing their responsiveness to gamma interferon. , 1985, The Journal of clinical investigation.

[69]  G. Green Pulmonary clearance of infectious agents. , 1968, Annual review of medicine.

[70]  E. C. Pielou The measurement of diversity in different types of biological collections , 1966 .

[71]  J. T. Curtis,et al.  An Ordination of the Upland Forest Communities of Southern Wisconsin , 1957 .