Skip to main content
Top
Published in: Respiratory Research 1/2020

Open Access 01-12-2020 | Streptococci | Research

The sputum microbiome is distinct between COPD and health, independent of smoking history

Authors: Koirobi Haldar, Leena George, Zhang Wang, Vijay Mistry, Mohammadali Yavari Ramsheh, Robert C. Free, Catherine John, Nicola F. Reeve, Bruce E. Miller, Ruth Tal-Singer, Adam J. Webb, Anthony J. Brookes, Martin D. Tobin, Dave Singh, Gavin C. Donaldson, Jadwiga A. Wedzicha, James R. Brown, Michael R. Barer, Christopher E. Brightling

Published in: Respiratory Research | Issue 1/2020

Login to get access

Abstract

Background

Airway bacterial dysbiosis is a feature of chronic obstructive pulmonary disease (COPD). However, there is limited comparative data of the lung microbiome between healthy smokers, non-smokers and COPD.

Methods

We compared the 16S rRNA gene-based sputum microbiome generated from pair-ended Illumina sequencing of 124 healthy subjects (28 smokers and 96 non-smokers with normal lung function), with single stable samples from 218 COPD subjects collected from three UK clinical centres as part of the COPDMAP consortium.

Results

In healthy subjects Firmicutes, Bacteroidetes and Actinobacteria were the major phyla constituting 88% of the total reads, and Streptococcus, Veillonella, Prevotella, Actinomyces and Rothia were the dominant genera. Haemophilus formed only 3% of the healthy microbiome. In contrast, Proteobacteria was the most dominant phylum accounting for 50% of the microbiome in COPD subjects, with Haemophilus and Moraxella at genus level contributing 25 and 3% respectively. There were no differences in the microbiome profile within healthy and COPD subgroups when stratified based on smoking history. Principal coordinate analysis on operational taxonomic units showed two distinct clusters, representative of healthy and COPD subjects (PERMANOVA, p = 0·001).

Conclusion

The healthy and COPD sputum microbiomes are distinct and independent of smoking history. Our results underline the important role for Gammaproteobacteria in COPD.
Appendix
Available only for authorised users
Literature
1.
go back to reference Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008;359(22):2355–65.CrossRef Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 2008;359(22):2355–65.CrossRef
2.
go back to reference Dickson RP, Martinez FJ, Huffnagle GB. The role of the microbiome in exacerbations of chronic lung diseases. Lancet. 2014;384(9944):691–702.CrossRef Dickson RP, Martinez FJ, Huffnagle GB. The role of the microbiome in exacerbations of chronic lung diseases. Lancet. 2014;384(9944):691–702.CrossRef
3.
go back to reference Erb-Downward JR, Thompson DL, Han MK, Freeman CM, McCloskey L, Schmidt LA, et al. Analysis of the lung microbiome in the "healthy" smoker and in COPD. PLoS One. 2011;6(2):e16384.CrossRef Erb-Downward JR, Thompson DL, Han MK, Freeman CM, McCloskey L, Schmidt LA, et al. Analysis of the lung microbiome in the "healthy" smoker and in COPD. PLoS One. 2011;6(2):e16384.CrossRef
4.
go back to reference Pragman AA, Kim HB, Reilly CS, Wendt C, Isaacson RE. The lung microbiome in moderate and severe chronic obstructive pulmonary disease. PLoS One. 2012;7(10):e47305.CrossRef Pragman AA, Kim HB, Reilly CS, Wendt C, Isaacson RE. The lung microbiome in moderate and severe chronic obstructive pulmonary disease. PLoS One. 2012;7(10):e47305.CrossRef
5.
go back to reference Hilty M, Burke C, Pedro H, Cardenas P, Bush A, Bossley C, et al. Disordered microbial communities in asthmatic airways. PLoS One. 2010;5(1):e8578.CrossRef Hilty M, Burke C, Pedro H, Cardenas P, Bush A, Bossley C, et al. Disordered microbial communities in asthmatic airways. PLoS One. 2010;5(1):e8578.CrossRef
6.
go back to reference Einarsson GG, Comer DM, McIlreavey L, Parkhill J, Ennis M, Tunney MM, et al. Community dynamics and the lower airway microbiota in stable chronic obstructive pulmonary disease, smokers and healthy non-smokers. Thorax. 2016;71(9):795–803.CrossRef Einarsson GG, Comer DM, McIlreavey L, Parkhill J, Ennis M, Tunney MM, et al. Community dynamics and the lower airway microbiota in stable chronic obstructive pulmonary disease, smokers and healthy non-smokers. Thorax. 2016;71(9):795–803.CrossRef
7.
go back to reference Cabrera-Rubio R, Garcia-Núñez M, Setó L, Antó JM, Moya A, Monsó E, et al. Microbiome diversity in the bronchial tracts of patients with chronic obstructive pulmonary disease. J Clin Microbiol. 2012;50(11):3562–8.CrossRef Cabrera-Rubio R, Garcia-Núñez M, Setó L, Antó JM, Moya A, Monsó E, et al. Microbiome diversity in the bronchial tracts of patients with chronic obstructive pulmonary disease. J Clin Microbiol. 2012;50(11):3562–8.CrossRef
8.
go back to reference Huang YJ, Sethi S, Murphy T, Nariya S, Boushey HA, Lynch SV. Airway microbiome dynamics in exacerbations of chronic obstructive pulmonary disease. J Clin Microbiol. 2014;52:2813–23.CrossRef Huang YJ, Sethi S, Murphy T, Nariya S, Boushey HA, Lynch SV. Airway microbiome dynamics in exacerbations of chronic obstructive pulmonary disease. J Clin Microbiol. 2014;52:2813–23.CrossRef
9.
go back to reference Wang Z, Bafadhel M, Haldar K, Spivak A, Mayhew D, Miller BE, et al. Lung microbiome dynamics in COPD exacerbations. Eur Respir J. 2016;47(4):1082–92.CrossRef Wang Z, Bafadhel M, Haldar K, Spivak A, Mayhew D, Miller BE, et al. Lung microbiome dynamics in COPD exacerbations. Eur Respir J. 2016;47(4):1082–92.CrossRef
10.
go back to reference Haldar K, Bafadhel M, Lau K, Berg A, Kwambana B, Kebadze T, et al. Microbiome balance in sputum determined by PCR stratifies COPD exacerbations and shows potential for selective use of antibiotics. PLoS One. 2017;12(8):e0182833.CrossRef Haldar K, Bafadhel M, Lau K, Berg A, Kwambana B, Kebadze T, et al. Microbiome balance in sputum determined by PCR stratifies COPD exacerbations and shows potential for selective use of antibiotics. PLoS One. 2017;12(8):e0182833.CrossRef
11.
go back to reference Charlson ES, Chen J, Custers-Allen R, Bittinger K, Li H, Sinha R, et al. Disordered microbial communities in the upper respiratory tract of cigarette smokers. PLoS One. 2010;5(12):e15216.CrossRef Charlson ES, Chen J, Custers-Allen R, Bittinger K, Li H, Sinha R, et al. Disordered microbial communities in the upper respiratory tract of cigarette smokers. PLoS One. 2010;5(12):e15216.CrossRef
12.
go back to reference Johannessen A, Omenaas ER, Bakke PS, Gulsvik A. Implications of reversibility testing on prevalence and risk factors for chronic obstructive pulmonary disease: a community study. Thorax. 2005;60(10):842–7.CrossRef Johannessen A, Omenaas ER, Bakke PS, Gulsvik A. Implications of reversibility testing on prevalence and risk factors for chronic obstructive pulmonary disease: a community study. Thorax. 2005;60(10):842–7.CrossRef
13.
go back to reference Wang Z, Singh R, Miller BE, Tal-Singer R, Van Horn S, Tomsho L, et al. Sputum microbiome temporal variability and dysbiosis in chronic obstructive pulmonary disease exacerbations: an analysis of the COPDMAP study. Thorax. 2018;73(4):331–8.CrossRef Wang Z, Singh R, Miller BE, Tal-Singer R, Van Horn S, Tomsho L, et al. Sputum microbiome temporal variability and dysbiosis in chronic obstructive pulmonary disease exacerbations: an analysis of the COPDMAP study. Thorax. 2018;73(4):331–8.CrossRef
14.
go back to reference Kuczynski J, Stombaugh J, Walters WA, González A, Caporaso JG, Knight R. Using QIIME to analyze 16S rRNA gene sequences from microbial communities. Curr Protoc Microbiol. 2012;27:1E–5. Kuczynski J, Stombaugh J, Walters WA, González A, Caporaso JG, Knight R. Using QIIME to analyze 16S rRNA gene sequences from microbial communities. Curr Protoc Microbiol. 2012;27:1E–5.
15.
go back to reference Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114–20.CrossRef Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114–20.CrossRef
17.
go back to reference Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R. UCHIME improves sensitivity and speed of chimera detection. Bioinformatics. 2011;27(16):2194–200.CrossRef Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R. UCHIME improves sensitivity and speed of chimera detection. Bioinformatics. 2011;27(16):2194–200.CrossRef
18.
go back to reference Wang Q, Garrity GM, Tiedje JM, Cole JR. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol. 2007;73(16):5261–7.CrossRef Wang Q, Garrity GM, Tiedje JM, Cole JR. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol. 2007;73(16):5261–7.CrossRef
19.
go back to reference Lozupone C, Knight R. UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol. 2005;71(12):8228–35.CrossRef Lozupone C, Knight R. UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol. 2005;71(12):8228–35.CrossRef
20.
go back to reference Langille MGI, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotech. 2013;31(9):814–21.CrossRef Langille MGI, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, et al. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotech. 2013;31(9):814–21.CrossRef
21.
go back to reference Parks DH, Tyson GW, Hugenholtz P, Beiko RG. STAMP: statistical analysis of taxonomic and functional profiles. Bioinformatics. 2014;30(21):3123–4.CrossRef Parks DH, Tyson GW, Hugenholtz P, Beiko RG. STAMP: statistical analysis of taxonomic and functional profiles. Bioinformatics. 2014;30(21):3123–4.CrossRef
22.
go back to reference Anderson MJ. A new method for non-parametric multivariate analysis of variance. Aust Ecol. 2001;26(1):32–46. Anderson MJ. A new method for non-parametric multivariate analysis of variance. Aust Ecol. 2001;26(1):32–46.
23.
go back to reference Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12(6):R60.CrossRef Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12(6):R60.CrossRef
24.
go back to reference Bergen B, Endres S, Engel A, Zark M, Dittmar T, Sommer U, et al. Acidification and warming affect prominent bacteria in two seasonal phytoplankton bloom mesocosms. Environ Microbiol. 2016;18(12):4579–95.CrossRef Bergen B, Endres S, Engel A, Zark M, Dittmar T, Sommer U, et al. Acidification and warming affect prominent bacteria in two seasonal phytoplankton bloom mesocosms. Environ Microbiol. 2016;18(12):4579–95.CrossRef
25.
go back to reference Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, Ward DV, et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 2012;13(9):R79.CrossRef Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, Ward DV, et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 2012;13(9):R79.CrossRef
26.
go back to reference Diao W, Shen N, Du Y, Erb-Downward JR, Sun X, Guo C, et al. Symptom-related sputum microbiota in stable chronic obstructive pulmonary disease. Int J Chronic Obstruct Pulmon Dis. 2018;13:2289–99.CrossRef Diao W, Shen N, Du Y, Erb-Downward JR, Sun X, Guo C, et al. Symptom-related sputum microbiota in stable chronic obstructive pulmonary disease. Int J Chronic Obstruct Pulmon Dis. 2018;13:2289–99.CrossRef
27.
go back to reference Sze MA, Dimitriu PA, Hayashi S, Elliott WM, McDonough JE, Gosselink JV, et al. The lung tissue microbiome in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;185(10):1073–80.CrossRef Sze MA, Dimitriu PA, Hayashi S, Elliott WM, McDonough JE, Gosselink JV, et al. The lung tissue microbiome in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;185(10):1073–80.CrossRef
28.
go back to reference Pragman AA, Lyu T, Baller JA, Gould TJ, Kelly RF, Reilly CS, et al. The lung tissue microbiota of mild and moderate chronic obstructive pulmonary disease. Microbiome. 2018;6:7.CrossRef Pragman AA, Lyu T, Baller JA, Gould TJ, Kelly RF, Reilly CS, et al. The lung tissue microbiota of mild and moderate chronic obstructive pulmonary disease. Microbiome. 2018;6:7.CrossRef
29.
go back to reference Pragman AA, Kim HB, Reilly CS, Wendt C, Isaacson RE. Chronic obstructive pulmonary disease lung microbiota diversity may be mediated by age or inhaled corticosteroid use. J Clin Microbiol. 2015;53:1050.CrossRef Pragman AA, Kim HB, Reilly CS, Wendt C, Isaacson RE. Chronic obstructive pulmonary disease lung microbiota diversity may be mediated by age or inhaled corticosteroid use. J Clin Microbiol. 2015;53:1050.CrossRef
30.
go back to reference Morris A, Beck JM, Schloss PD, Campbell TB, Crothers K, Curtis JL, et al. Comparison of the respiratory microbiome in healthy nonsmokers and smokers. Am J Respir Crit Care Med. 2013;187(10):1067–75.CrossRef Morris A, Beck JM, Schloss PD, Campbell TB, Crothers K, Curtis JL, et al. Comparison of the respiratory microbiome in healthy nonsmokers and smokers. Am J Respir Crit Care Med. 2013;187(10):1067–75.CrossRef
31.
go back to reference Shukla SD, Walters EH, Simpson JL, Keely S, Wark PAB, O’Toole RF, et al. Hypoxia-inducible factor and bacterial infections in chronic obstructive pulmonary disease. Respirology. 2020;25(1):53–63.CrossRef Shukla SD, Walters EH, Simpson JL, Keely S, Wark PAB, O’Toole RF, et al. Hypoxia-inducible factor and bacterial infections in chronic obstructive pulmonary disease. Respirology. 2020;25(1):53–63.CrossRef
32.
go back to reference Bafadhel M, Haldar K, Barker B, Patel H, Mistry V, Barer MR, et al. Airway bacteria measured by quantitative polymerase chain reaction and culture in patients with stable COPD: relationship with neutrophilic airway inflammation, exacerbation frequency, and lung function. Int J Chron Obstruct Pulmon Dis. 2015;10:1075–83.CrossRef Bafadhel M, Haldar K, Barker B, Patel H, Mistry V, Barer MR, et al. Airway bacteria measured by quantitative polymerase chain reaction and culture in patients with stable COPD: relationship with neutrophilic airway inflammation, exacerbation frequency, and lung function. Int J Chron Obstruct Pulmon Dis. 2015;10:1075–83.CrossRef
Metadata
Title
The sputum microbiome is distinct between COPD and health, independent of smoking history
Authors
Koirobi Haldar
Leena George
Zhang Wang
Vijay Mistry
Mohammadali Yavari Ramsheh
Robert C. Free
Catherine John
Nicola F. Reeve
Bruce E. Miller
Ruth Tal-Singer
Adam J. Webb
Anthony J. Brookes
Martin D. Tobin
Dave Singh
Gavin C. Donaldson
Jadwiga A. Wedzicha
James R. Brown
Michael R. Barer
Christopher E. Brightling
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-01448-3

Other articles of this Issue 1/2020

Respiratory Research 1/2020 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.