{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T10:23:28Z","timestamp":1768818208736,"version":"3.49.0"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BPD\/120777\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/120777\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["IF\/00764\/2013"],"award-info":[{"award-number":["IF\/00764\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Young Investigator Prize Francisco Augusto da Fonseca Dias and Maria Jos\u00e9 Melenas da Fonseca Dias"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The lung is inhabited by a diverse microbiome that originates from the oropharynx by a mechanism of micro-aspiration. Its bacterial biomass is usually low; however, this condition shifts in lung cancer (LC), chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). These chronic lung disorders (CLD) may coexist in the same patient as comorbidities and share common risk factors, among which the microbiome is included. We characterized the microbiome of 106 bronchoalveolar lavages. Samples were initially subdivided into cancer and non-cancer and high-throughput sequenced for the 16S rRNA gene. Additionally, we used a cohort of 25 CLD patients where crossed comorbidities were excluded. Firmicutes, Proteobacteria and Bacteroidetes were the most prevalent phyla independently of the analyzed group. <jats:italic>Streptococcus<\/jats:italic> and <jats:italic>Prevotella<\/jats:italic> were associated with LC and <jats:italic>Haemophilus<\/jats:italic> was enhanced in COPD versus ILD. Although no significant discrepancies in microbial diversity were observed between cancer and non-cancer samples, statistical tests suggested a gradient across CLD where COPD and ILD displayed the highest and lowest alpha diversities, respectively. Moreover, COPD and ILD were separated in two clusters by the unweighted UniFrac distance (<jats:italic>P<\/jats:italic> value\u2009=\u20090.0068). Our results support the association of <jats:italic>Streptoccocus<\/jats:italic> and <jats:italic>Prevotella<\/jats:italic> with LC and of <jats:italic>Haemophilus<\/jats:italic> with COPD, and advocate for specific CLD signatures.<\/jats:p>","DOI":"10.1038\/s41598-021-94468-y","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T10:04:09Z","timestamp":1626948249000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Comparative analysis of the bronchoalveolar microbiome in Portuguese patients with different chronic lung disorders"],"prefix":"10.1038","volume":"11","author":[{"given":"Susana","family":"Seixas","sequence":"first","affiliation":[]},{"given":"Allison R.","family":"Kolbe","sequence":"additional","affiliation":[]},{"given":"S\u00edlvia","family":"Gomes","sequence":"additional","affiliation":[]},{"given":"Maria","family":"Sucena","sequence":"additional","affiliation":[]},{"given":"Catarina","family":"Sousa","sequence":"additional","affiliation":[]},{"given":"Lu\u00eds","family":"Vaz Rodrigues","sequence":"additional","affiliation":[]},{"given":"Gilberto","family":"Teixeira","sequence":"additional","affiliation":[]},{"given":"Paula","family":"Pinto","sequence":"additional","affiliation":[]},{"given":"Tiago","family":"Tavares de Abreu","sequence":"additional","affiliation":[]},{"given":"Cristina","family":"B\u00e1rbara","sequence":"additional","affiliation":[]},{"given":"J\u00falio","family":"Semedo","sequence":"additional","affiliation":[]},{"given":"Leonor","family":"Mota","sequence":"additional","affiliation":[]},{"given":"Ana Sofia","family":"Carvalho","sequence":"additional","affiliation":[]},{"given":"Rune","family":"Matthiesen","sequence":"additional","affiliation":[]},{"given":"Patr\u00edcia Isabel","family":"Marques","sequence":"additional","affiliation":[]},{"given":"Marcos","family":"P\u00e9rez-Losada","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"key":"94468_CR1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004923","volume":"11","author":"RP Dickson","year":"2015","unstructured":"Dickson, R. P. & Huffnagle, G. B. The lung microbiome: New principles for respiratory bacteriology in health and disease. PLoS Pathog 11, e1004923. https:\/\/doi.org\/10.1371\/journal.ppat.1004923 (2015).","journal-title":"PLoS Pathog"},{"key":"94468_CR2","unstructured":"The Lung Microbiome. (2019)."},{"key":"94468_CR3","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/s2213-2600(14)70028-1","volume":"2","author":"RP Dickson","year":"2014","unstructured":"Dickson, R. P., Erb-Downward, J. R. & Huffnagle, G. B. Towards an ecology of the lung: New conceptual models of pulmonary microbiology and pneumonia pathogenesis. Lancet Respir. Med. 2, 238\u2013246. https:\/\/doi.org\/10.1016\/s2213-2600(14)70028-1 (2014).","journal-title":"Lancet Respir. Med."},{"key":"94468_CR4","doi-asserted-by":"publisher","first-page":"1602467","DOI":"10.1183\/13993003.02467-2016","volume":"50","author":"NDJ Ubags","year":"2017","unstructured":"Ubags, N. D. J. & Marsland, B. J. Mechanistic insight into the function of the microbiome in lung diseases. Eur. Respir. J. 50, 1602467. https:\/\/doi.org\/10.1183\/13993003.02467-2016 (2017).","journal-title":"Eur. Respir. J."},{"key":"94468_CR5","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/mi.2016.108","volume":"10","author":"GB Huffnagle","year":"2017","unstructured":"Huffnagle, G. B., Dickson, R. P. & Lukacs, N. W. The respiratory tract microbiome and lung inflammation: A two-way street. Mucosal. Immunol. 10, 299\u2013306. https:\/\/doi.org\/10.1038\/mi.2016.108 (2017).","journal-title":"Mucosal. Immunol."},{"key":"94468_CR6","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1183\/09031936.00062212","volume":"42","author":"S Laroumagne","year":"2013","unstructured":"Laroumagne, S. et al. Bronchial colonisation in patients with lung cancer: A prospective study. Eur. Respir. J. 42, 220\u2013229. https:\/\/doi.org\/10.1183\/09031936.00062212 (2013).","journal-title":"Eur. Respir. J."},{"key":"94468_CR7","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00214-2017","author":"CF Vogelmeier","year":"2017","unstructured":"Vogelmeier, C. F. et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary. Eur. Respir. J. https:\/\/doi.org\/10.1183\/13993003.00214-2017 (2017).","journal-title":"Eur. Respir. J."},{"key":"94468_CR8","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1183\/09031936.04.00014304","volume":"23","author":"BR Celli","year":"2004","unstructured":"Celli, B. R. et al. Standards for the diagnosis and treatment of patients with COPD: A summary of the ATS\/ERS position paper. Eur. Respir. J. 23, 932\u2013946. https:\/\/doi.org\/10.1183\/09031936.04.00014304 (2004).","journal-title":"Eur. Respir. J."},{"key":"94468_CR9","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2017-210408","author":"D Mayhew","year":"2018","unstructured":"Mayhew, D. et al. Longitudinal profiling of the lung microbiome in the AERIS study demonstrates repeatability of bacterial and eosinophilic COPD exacerbations. Thorax https:\/\/doi.org\/10.1136\/thoraxjnl-2017-210408 (2018).","journal-title":"Thorax"},{"key":"94468_CR10","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1183\/13993003.01406-2015","volume":"47","author":"Z Wang","year":"2016","unstructured":"Wang, Z. et al. Lung microbiome dynamics in COPD exacerbations. Eur. Respir. J. 47, 1082\u20131092. https:\/\/doi.org\/10.1183\/13993003.01406-2015 (2016).","journal-title":"Eur. Respir. J."},{"key":"94468_CR11","doi-asserted-by":"publisher","first-page":"s71","DOI":"10.7861\/clinmedicine.16-6-s71","volume":"16","author":"TA Mikolasch","year":"2016","unstructured":"Mikolasch, T. A., Garthwaite, H. S. & Porter, J. C. Update in diagnosis and management of interstitial lung disease. Clin. Med. (Lond.) 16, s71\u2013s78. https:\/\/doi.org\/10.7861\/clinmedicine.16-6-s71 (2016).","journal-title":"Clin. Med. (Lond.)"},{"key":"94468_CR12","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1164\/rccm.201403-0541OC","volume":"190","author":"PL Molyneaux","year":"2014","unstructured":"Molyneaux, P. L. et al. The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 190, 906\u2013913. https:\/\/doi.org\/10.1164\/rccm.201403-0541OC (2014).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"94468_CR13","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s12931-017-0511-3","volume":"18","author":"PL Molyneaux","year":"2017","unstructured":"Molyneaux, P. L. et al. Changes in the respiratory microbiome during acute exacerbations of idiopathic pulmonary fibrosis. Respir. Res. 18, 29. https:\/\/doi.org\/10.1186\/s12931-017-0511-3 (2017).","journal-title":"Respir. Res."},{"key":"94468_CR14","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394\u2013424. https:\/\/doi.org\/10.3322\/caac.21492 (2018).","journal-title":"CA Cancer J. Clin."},{"key":"94468_CR15","unstructured":"Hardavella, G. & Sethi, T. In Lung Cancer (eds Dingemans, A. M. C., Reck, M. & Westeel, V.) 285 (2015)."},{"key":"94468_CR16","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1002\/ijc.31098","volume":"142","author":"HX Liu","year":"2018","unstructured":"Liu, H. X. et al. Difference of lower airway microbiome in bilateral protected specimen brush between lung cancer patients with unilateral lobar masses and control subjects. Int. J. Cancer  142, 769\u2013778. https:\/\/doi.org\/10.1002\/ijc.31098 (2018).","journal-title":"Int. J. Cancer"},{"key":"94468_CR17","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1186\/s13059-016-1021-1","volume":"17","author":"G Yu","year":"2016","unstructured":"Yu, G. et al. Characterizing human lung tissue microbiota and its relationship to epidemiological and clinical features. Genome Biol. 17, 163. https:\/\/doi.org\/10.1186\/s13059-016-1021-1 (2016).","journal-title":"Genome Biol."},{"key":"94468_CR18","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1164\/rccm.201710-2118OC","volume":"198","author":"JJ Tsay","year":"2018","unstructured":"Tsay, J. J. et al. Airway microbiota is associated with upregulation of the PI3K pathway in lung cancer. Am. J. Respir. Crit. Care Med. 198, 1188\u20131198. https:\/\/doi.org\/10.1164\/rccm.201710-2118OC (2018).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"94468_CR19","doi-asserted-by":"publisher","first-page":"12838","DOI":"10.1038\/s41598-019-49195-w","volume":"9","author":"S Gomes","year":"2019","unstructured":"Gomes, S. et al. Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma. Sci. Rep. 9, 12838. https:\/\/doi.org\/10.1038\/s41598-019-49195-w (2019).","journal-title":"Sci. Rep."},{"key":"94468_CR20","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1183\/09031936.00186914","volume":"45","author":"S Meiners","year":"2015","unstructured":"Meiners, S., Eickelberg, O. & Konigshoff, M. Hallmarks of the ageing lung. Eur. Respir. J. 45, 807\u2013827. https:\/\/doi.org\/10.1183\/09031936.00186914 (2015).","journal-title":"Eur. Respir. J."},{"key":"94468_CR21","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.pupt.2013.05.003","volume":"26","author":"K Vermaelen","year":"2013","unstructured":"Vermaelen, K. & Brusselle, G. Exposing a deadly alliance: Novel insights into the biological links between COPD and lung cancer. Pulm. Pharmacol. Ther. 26, 544\u2013554. https:\/\/doi.org\/10.1016\/j.pupt.2013.05.003 (2013).","journal-title":"Pulm. Pharmacol. Ther."},{"key":"94468_CR22","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1164\/rccm.201711-2180OC","volume":"198","author":"RP Dickson","year":"2018","unstructured":"Dickson, R. P. et al. The lung microbiota of healthy mice are highly variable, cluster by environment, and reflect variation in baseline lung innate immunity. Am. J. Respir. Crit. Care Med. 198, 497\u2013508. https:\/\/doi.org\/10.1164\/rccm.201711-2180OC (2018).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"94468_CR23","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.rmed.2019.04.009","volume":"152","author":"AL Frank","year":"2019","unstructured":"Frank, A. L., Kreuter, M. & Schwarzkopf, L. Economic burden of incident interstitial lung disease (ILD) and the impact of comorbidity on costs of care. Respir. Med. 152, 25\u201331. https:\/\/doi.org\/10.1016\/j.rmed.2019.04.009 (2019).","journal-title":"Respir. Med."},{"key":"94468_CR24","unstructured":"Lung Cancer. (2015)."},{"key":"94468_CR25","doi-asserted-by":"publisher","first-page":"42190","DOI":"10.1038\/srep42190","volume":"7","author":"AS Carvalho","year":"2017","unstructured":"Carvalho, A. S. et al. Bronchoalveolar lavage proteomics in patients with suspected lung cancer. Sci. Rep. 7, 42190. https:\/\/doi.org\/10.1038\/srep42190 (2017).","journal-title":"Sci. Rep."},{"key":"94468_CR26","doi-asserted-by":"publisher","first-page":"5112","DOI":"10.1128\/AEM.01043-13","volume":"79","author":"JJ Kozich","year":"2013","unstructured":"Kozich, J. J., Westcott, S. L., Baxter, N. T., Highlander, S. K. & Schloss, P. D. Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform. Appl. Environ. Microbiol. 79, 5112\u20135120. https:\/\/doi.org\/10.1128\/AEM.01043-13 (2013).","journal-title":"Appl. Environ. Microbiol."},{"key":"94468_CR27","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nmeth.3869","volume":"13","author":"BJ Callahan","year":"2016","unstructured":"Callahan, B. J. et al. DADA2: High-resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581\u2013583. https:\/\/doi.org\/10.1038\/nmeth.3869 (2016).","journal-title":"Nat. Methods"},{"key":"94468_CR28","doi-asserted-by":"publisher","first-page":"D590","DOI":"10.1093\/nar\/gks1219","volume":"41","author":"C Quast","year":"2013","unstructured":"Quast, C. et al. The SILVA ribosomal RNA gene database project: Improved data processing and web-based tools. Nucleic Acids Res. 41, D590-596. https:\/\/doi.org\/10.1093\/nar\/gks1219 (2013).","journal-title":"Nucleic Acids Res."},{"key":"94468_CR29","doi-asserted-by":"publisher","first-page":"5261","DOI":"10.1128\/AEM.00062-07","volume":"73","author":"Q Wang","year":"2007","unstructured":"Wang, Q., Garrity, G. M., Tiedje, J. M. & Cole, J. R. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl. Environ. Microbiol. 73, 5261\u20135267. https:\/\/doi.org\/10.1128\/AEM.00062-07 (2007).","journal-title":"Appl. Environ. Microbiol."},{"key":"94468_CR30","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1093\/molbev\/mst010","volume":"30","author":"K Katoh","year":"2013","unstructured":"Katoh, K. & Standley, D. M. MAFFT multiple sequence alignment software version 7: Improvements in performance and usability. Mol. Biol. Evol. 30, 772\u2013780. https:\/\/doi.org\/10.1093\/molbev\/mst010 (2013).","journal-title":"Mol. Biol. Evol."},{"key":"94468_CR31","doi-asserted-by":"publisher","first-page":"e9490","DOI":"10.1371\/journal.pone.0009490","volume":"5","author":"MN Price","year":"2010","unstructured":"Price, M. N., Dehal, P. S. & Arkin, A. P. FastTree 2\u2013approximately maximum-likelihood trees for large alignments. PLoS ONE 5, e9490. https:\/\/doi.org\/10.1371\/journal.pone.0009490 (2010).","journal-title":"PLoS ONE"},{"key":"94468_CR32","doi-asserted-by":"publisher","first-page":"e61217","DOI":"10.1371\/journal.pone.0061217","volume":"8","author":"PJ McMurdie","year":"2013","unstructured":"McMurdie, P. J. & Holmes, S. phyloseq: An R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE 8, e61217. https:\/\/doi.org\/10.1371\/journal.pone.0061217 (2013).","journal-title":"PLoS ONE"},{"key":"94468_CR33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003531","volume":"10","author":"PJ McMurdie","year":"2014","unstructured":"McMurdie, P. J. & Holmes, S. Waste not, want not: Why rarefying microbiome data is inadmissible. PLoS Comput. Biol. 10, e1003531. https:\/\/doi.org\/10.1371\/journal.pcbi.1003531 (2014).","journal-title":"PLoS Comput. Biol."},{"key":"94468_CR34","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15, 550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8 (2014).","journal-title":"Genome Biol"},{"key":"94468_CR35","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s40168-017-0237-y","volume":"5","author":"S Weiss","year":"2017","unstructured":"Weiss, S. et al. Normalization and microbial differential abundance strategies depend upon data characteristics. Microbiome 5, 27. https:\/\/doi.org\/10.1186\/s40168-017-0237-y (2017).","journal-title":"Microbiome"},{"key":"94468_CR36","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1111\/j.1654-1103.2003.tb02228.x","volume":"14","author":"P Dixon","year":"2003","unstructured":"Dixon, P. VEGAN, a package of R functions for community ecology. J. Veg. Sci. 14, 927\u2013930 (2003).","journal-title":"J. Veg. Sci."},{"key":"94468_CR37","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B (Methodol.) 57, 289\u2013300. https:\/\/doi.org\/10.1111\/j.2517-6161.1995.tb02031.x (1995).","journal-title":"J. R. Stat. Soc. Ser. B (Methodol.)"},{"key":"94468_CR38","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1080\/00401706.1977.10489493","volume":"19","author":"RD Cook","year":"1977","unstructured":"Cook, R. D. Detection of influential observation in linear regression. Technometrics 19, 15\u201318. https:\/\/doi.org\/10.1080\/00401706.1977.10489493 (1977).","journal-title":"Technometrics"},{"key":"94468_CR39","volume-title":"Statistical Power Analysis for the Behavioral Sciences","author":"J Cohen","year":"1988","unstructured":"Cohen, J. Statistical Power Analysis for the Behavioral Sciences 2nd edn. (Lawrence Earlbaum Associates, Hillsdale, 1988).","edition":"2"},{"key":"94468_CR40","unstructured":"Team, R. D. C. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, Vienna, Austria, 2008)."},{"key":"94468_CR41","unstructured":"RStudio, R. T. Integrated development for R. RStudio, IncBoston, MA (2015)."},{"key":"94468_CR42","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/s2213-2600(14)70069-4","volume":"2","author":"MK Han","year":"2014","unstructured":"Han, M. K. et al. Lung microbiome and disease progression in idiopathic pulmonary fibrosis: An analysis of the COMET study. Lancet Respir. Med. 2, 548\u2013556. https:\/\/doi.org\/10.1016\/s2213-2600(14)70069-4 (2014).","journal-title":"Lancet Respir. Med."},{"key":"94468_CR43","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1007\/s12272-017-0933-y","volume":"40","author":"GL Kim","year":"2017","unstructured":"Kim, G. L., Seon, S. H. & Rhee, D. K. Pneumonia and Streptococcus pneumoniae vaccine. Arch. Pharm. Res. 40, 885\u2013893. https:\/\/doi.org\/10.1007\/s12272-017-0933-y (2017).","journal-title":"Arch. Pharm. Res."},{"key":"94468_CR44","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/2049-2618-1-19","volume":"1","author":"LN Segal","year":"2013","unstructured":"Segal, L. N. et al. Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation. Microbiome 1, 19. https:\/\/doi.org\/10.1186\/2049-2618-1-19 (2013).","journal-title":"Microbiome"},{"key":"94468_CR45","doi-asserted-by":"publisher","first-page":"16031","DOI":"10.1038\/nmicrobiol.2016.31","volume":"1","author":"LN Segal","year":"2016","unstructured":"Segal, L. N. et al. Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nat. Microbiol. 1, 16031. https:\/\/doi.org\/10.1038\/nmicrobiol.2016.31 (2016).","journal-title":"Nat. Microbiol."},{"key":"94468_CR46","doi-asserted-by":"publisher","unstructured":"Yang, D. et al. Dysregulated lung commensal bacteria drive interleukin-17b production to promote pulmonary fibrosis through their outer membrane vesicles. Immunity 50, 692\u2013706 e697. https:\/\/doi.org\/10.1016\/j.immuni.2019.02.001 (2019).","DOI":"10.1016\/j.immuni.2019.02.001"},{"key":"94468_CR47","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s12943-016-0551-1","volume":"15","author":"EA Marshall","year":"2016","unstructured":"Marshall, E. A. et al. Emerging roles of T helper 17 and regulatory T cells in lung cancer progression and metastasis. Mol. Cancer 15, 67. https:\/\/doi.org\/10.1186\/s12943-016-0551-1 (2016).","journal-title":"Mol. Cancer"},{"key":"94468_CR48","doi-asserted-by":"publisher","first-page":"00015","DOI":"10.1183\/23120541.00015-2018","volume":"4","author":"M Mika","year":"2018","unstructured":"Mika, M. et al. Microbial and host immune factors as drivers of COPD. ERJ Open Res. 4, 00015\u201302018. https:\/\/doi.org\/10.1183\/23120541.00015-2018 (2018).","journal-title":"ERJ Open Res."},{"key":"94468_CR49","doi-asserted-by":"publisher","first-page":"e31976","DOI":"10.1371\/journal.pone.0031976","volume":"7","author":"JM Larsen","year":"2012","unstructured":"Larsen, J. M. et al. Divergent pro-inflammatory profile of human dendritic cells in response to commensal and pathogenic bacteria associated with the airway microbiota. PLoS ONE 7, e31976. https:\/\/doi.org\/10.1371\/journal.pone.0031976 (2012).","journal-title":"PLoS ONE"},{"key":"94468_CR50","doi-asserted-by":"publisher","first-page":"706376","DOI":"10.1155\/2015\/706376","volume":"2015","author":"PT King","year":"2015","unstructured":"King, P. T. & Sharma, R. The lung immune response to nontypeable haemophilus influenzae (lung immunity to NTHi). J. Immunol. Res. 2015, 706376. https:\/\/doi.org\/10.1155\/2015\/706376 (2015).","journal-title":"J. Immunol. Res."},{"key":"94468_CR51","doi-asserted-by":"publisher","first-page":"e0120371","DOI":"10.1371\/journal.pone.0120371","volume":"10","author":"PT King","year":"2015","unstructured":"King, P. T. et al. Nontypeable Haemophilus influenzae induces sustained lung oxidative stress and protease expression. PLoS ONE 10, e0120371. https:\/\/doi.org\/10.1371\/journal.pone.0120371 (2015).","journal-title":"PLoS ONE"},{"key":"94468_CR52","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3389\/fmed.2018.00116","volume":"5","author":"CA Newton","year":"2018","unstructured":"Newton, C. A., Molyneaux, P. L. & Oldham, J. M. Clinical genetics in interstitial lung disease. Front. Med. (Lausanne) 5, 116. https:\/\/doi.org\/10.3389\/fmed.2018.00116 (2018).","journal-title":"Front. Med. (Lausanne)"},{"key":"94468_CR53","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1164\/rccm.201607-1525OC","volume":"196","author":"Y Huang","year":"2017","unstructured":"Huang, Y. et al. Microbes are associated with host innate immune response in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med 196, 208\u2013219. https:\/\/doi.org\/10.1164\/rccm.201607-1525OC (2017).","journal-title":"Am. J. Respir. Crit. Care Med"},{"key":"94468_CR54","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1038\/s41522-021-00185-9","volume":"7","author":"K Opron","year":"2021","unstructured":"Opron, K. et al. Lung microbiota associations with clinical features of COPD in the SPIROMICS cohort. NPJ. Biofilms Microbiomes 7, 14. https:\/\/doi.org\/10.1038\/s41522-021-00185-9 (2021).","journal-title":"NPJ. Biofilms Microbiomes"},{"key":"94468_CR55","unstructured":"Idiopathic Pulmonary Fibrosis. (2016)."},{"key":"94468_CR56","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01519-2019","author":"R Invernizzi","year":"2020","unstructured":"Invernizzi, R. et al. Bacterial burden in the lower airways predicts disease progression in idiopathic pulmonary fibrosis and is independent of radiological disease extent. Eur. Respir. J. https:\/\/doi.org\/10.1183\/13993003.01519-2019 (2020).","journal-title":"Eur. Respir. J."},{"key":"94468_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2016.12.008","author":"Y Abe","year":"2016","unstructured":"Abe, Y. et al. A severe pulmonary complication in a patient with COL4A1-related disorder: A case report. Eur. J. Med. Genet. https:\/\/doi.org\/10.1016\/j.ejmg.2016.12.008 (2016).","journal-title":"Eur. J. Med. Genet."},{"key":"94468_CR58","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.lungcan.2019.08.022","volume":"136","author":"J Jin","year":"2019","unstructured":"Jin, J. et al. Diminishing microbiome richness and distinction in the lower respiratory tract of lung cancer patients: A multiple comparative study design with independent validation. Lung Cancer 136, 129\u2013135. https:\/\/doi.org\/10.1016\/j.lungcan.2019.08.022 (2019).","journal-title":"Lung Cancer"},{"key":"94468_CR59","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1111\/all.13760","volume":"74","author":"PJ Barnes","year":"2019","unstructured":"Barnes, P. J. Inflammatory endotypes in COPD. Allergy 74, 1249\u20131256. https:\/\/doi.org\/10.1111\/all.13760 (2019).","journal-title":"Allergy"},{"key":"94468_CR60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.rmed.2019.08.012","volume":"157","author":"E Dima","year":"2019","unstructured":"Dima, E. et al. The lung microbiome dynamics between stability and exacerbation in chronic obstructive pulmonary disease (COPD): Current perspectives. Respir. Med. 157, 1\u20136. https:\/\/doi.org\/10.1016\/j.rmed.2019.08.012 (2019).","journal-title":"Respir. Med."},{"key":"94468_CR61","doi-asserted-by":"publisher","unstructured":"Ghebre, M. A. et al. Biological exacerbation clusters demonstrate asthma and chronic obstructive pulmonary disease overlap with distinct mediator and microbiome profiles. J. Allergy Clin. Immunol. 141, 2027\u20132036 e2012. https:\/\/doi.org\/10.1016\/j.jaci.2018.04.013 (2018).","DOI":"10.1016\/j.jaci.2018.04.013"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-94468-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-94468-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-94468-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T11:30:36Z","timestamp":1670067036000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-94468-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,22]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["94468"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-94468-y","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,22]]},"assertion":[{"value":"26 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15042"}}