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Cited by 973Chronic Obstructive Pulmonary Disease (COPD) ResearchOral microbiology and periodontitis researchGut microbiota and health

The DOI matches its Crossref record; 41 of the 42 references it cites were found in a registry or an index.

Analysis of the lung microbiome in the “healthy” smoker and in COPD.

Open access
Erb-Downward, John R., Thompson, Deborah L., Han, Meilan K., Freeman, Christine M., McCloskey, Lisa, Schmidt, Lindsay A., Young, Vincent B., Toews, Galen B., Curtis, Jeffrey L., Sundaram, Baskaran, Martinez, Fernando J., Huffnagle, Gary B.·2011·PLoS ONE
DOI 10.1371/journal.pone.0016384PMC PMC3043049
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Abstract

Although culture-independent techniques have shown that the lungs are not sterile, little is known about the lung microbiome in chronic obstructive pulmonary disease (COPD). We used pyrosequencing of 16S amplicons to analyze the lung microbiome in two ways: first, using bronchoalveolar lavage (BAL) to sample the distal bronchi and air-spaces; and second, by examining multiple discrete tissue sites in the lungs of six subjects removed at the time of transplantation. We performed BAL on three never-smokers (NS) with normal spirometry, seven smokers with normal spirometry ("healthy smokers", HS), and four subjects with COPD (CS). Bacterial 16 s sequences were found in all subjects, without significant quantitative differences between groups. Both taxonomy-based and taxonomy-independent approaches disclosed heterogeneity in the bacterial communities between HS subjects that was similar to that seen in healthy NS and two mild COPD patients. The moderate and severe COPD patients had very limited community diversity, which was also noted in 28% of the healthy subjects. Both approaches revealed extensive membership overlap between the bacterial communities of the three study groups. No genera were common within a group but unique across groups. Our data suggests the existence of a core pulmonary bacterial microbiome that includes Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, and Porphyromonas. Most strikingly, there were significant micro-anatomic differences in bacterial communities within the same lung of subjects with advanced COPD. These studies are further demonstration of the pulmonary microbiome and highlight global and micro-anatomic changes in these bacterial communities in severe COPD patients.

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Figures

Figure 1 16S qPCR of BAL Samples. The number of copies of bacterial 16S per ml of BAL fluid was measured by qPCR (as described in Methods and Materials). The samples were divided into three groups: healthy smoker (HS), COPD subject (CS), and never-smoker (NS); the individual samples are displayed along the x-axis (Mean ± SEM). Samples where run in duplicate with two 10-fold dilutions.
Figure 1 16S qPCR of BAL Samples. The number of copies of bacterial 16S per ml of BAL fluid was measured by qPCR (as described in Methods and Materials). The samples were divided into three groups: healthy smoker (HS), COPD subject (CS), and never-smoker (NS); the individual samples are displayed along the x-axis (Mean ± SEM). Samples where run in duplicate with two 10-fold dilutions.CC0 · PubMed Central
Figure 2 Taxonomic Classification of Bacterial Communities Present in the BAL. The V1-V3 region of the bacterial 16S genes were sequenced using 454-pyrosequencing and taxonomically classified using RDP Classifier. A. Phylum level classification of the 16S amplicons present in a given subject. B. Genus level classification of these amplicons. The numbers at the bottom of each pie chart identify the organisms which can be found in Table 3.
Figure 2 Taxonomic Classification of Bacterial Communities Present in the BAL. The V1-V3 region of the bacterial 16S genes were sequenced using 454-pyrosequencing and taxonomically classified using RDP Classifier. A. Phylum level classification of the 16S amplicons present in a given subject. B. Genus level classification of these amplicons. The numbers at the bottom of each pie chart identify the organisms which can be found in Table 3.CC0 · PubMed Central
Figure 3 Identification of Bacterial Community Membership Overlap in Subject BALs. The relative abundance of each genera present in the BAL of each subject are plotted together with the numbers along the x-axis corresponding to the rank from Table 3. The study subject is displayed along the z-axis and the relative abundance (as a percent) is displayed along the y-axis. The genera Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Veillonella and Prophyromonas are highlighted due to the dominance of these organisms within all of the subjects examined.
Figure 3 Identification of Bacterial Community Membership Overlap in Subject BALs. The relative abundance of each genera present in the BAL of each subject are plotted together with the numbers along the x-axis corresponding to the rank from Table 3. The study subject is displayed along the z-axis and the relative abundance (as a percent) is displayed along the y-axis. The genera Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Veillonella and Prophyromonas are highlighted due to the dominance of these organisms within all of the subjects examined.CC0 · PubMed Central
Figure 4 Bacterial Communities Present in Individual Lung Airways. A. Bacterial community profiles for an entire explanted lung lobe from subjects with severe COPD. The total aggregate genus level reads of samples taken from the right lung of subject CS#5, the right lung of subject CS#6, and the left lung of subject CS#6 were analyzed on a per lung basis and compared to the BAL of subject CS#4 (reproduced from Figure 2). B. Multiple samples were taken from lung explants (right lung, subject CS#5; both lungs, subject CS#6) at the time of elective transplantation. Samples were harvested from the regions of lung indicated by the arrows on the gray lung schematic. Pie diagrams depict the genus level classification of 16S sequences, and the CT images demonstrate the absence of bronchiectasis in the airways adjacent to where samples were obtained. The key for the nine most abundant organisms is provided below the lung schematic. The full community breakdown for each of the airways can be found in Table S1.
Figure 4 Bacterial Communities Present in Individual Lung Airways. A. Bacterial community profiles for an entire explanted lung lobe from subjects with severe COPD. The total aggregate genus level reads of samples taken from the right lung of subject CS#5, the right lung of subject CS#6, and the left lung of subject CS#6 were analyzed on a per lung basis and compared to the BAL of subject CS#4 (reproduced from Figure 2). B. Multiple samples were taken from lung explants (right lung, subject CS#5; both lungs, subject CS#6) at the time of elective transplantation. Samples were harvested from the regions of lung indicated by the arrows on the gray lung schematic. Pie diagrams depict the genus level classification of 16S sequences, and the CT images demonstrate the absence of bronchiectasis in the airways adjacent to where samples were obtained. The key for the nine most abundant organisms is provided below the lung schematic. The full community breakdown for each of the airways can be found in Table S1.CC0 · PubMed Central
Figure 5 Bacterial Distribution Throughout COPD Lung Explants. Bacterial communities were characterized in the airways from 5 lobes of 4 lung explants. Multiple samples (4-8) were taken throughout the lung explants at the time of elective transplantation. The barchart depicts the genus level classification of 16S sequences identified.
Figure 5 Bacterial Distribution Throughout COPD Lung Explants. Bacterial communities were characterized in the airways from 5 lobes of 4 lung explants. Multiple samples (4-8) were taken throughout the lung explants at the time of elective transplantation. The barchart depicts the genus level classification of 16S sequences identified.CC0 · PubMed Central
Figure 6 Cluster Analysis of the Bacterial Communities Sampled from Sites. A. Furthest-neighbor joining tree built on the Bray-Curtis distance and B. Biplot of the principle components analysis of the normalized bacterial communities from multiple anatomic sites in the lung explants.
Figure 6 Cluster Analysis of the Bacterial Communities Sampled from Sites. A. Furthest-neighbor joining tree built on the Bray-Curtis distance and B. Biplot of the principle components analysis of the normalized bacterial communities from multiple anatomic sites in the lung explants.CC0 · PubMed Central

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  1. C Fletcher, 1978, Community Health., J Epidemiol, 32, 282

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Metadata

Authors
Erb-Downward, J. R., Thompson, D. L., Han, M. K., Freeman, C. M., McCloskey, L., Schmidt, L. A., Young, V. B., Toews, G. B., Curtis, J. L., Sundaram, B., Martinez, F. J., & Huffnagle, G. B.
Affiliations
University of Michigan (US)
Corresponding author
Huffnagle, Gary B.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2011-02-22
Volume
6
Issue
2
Pages
e16384
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0016384
PMC
PMC3043049
OpenAlex
W2163401084
Cited by
973
References
42
Citations by year
2026: 32 · 2025: 50 · 2024: 59 · 2023: 66 · 2022: 73 · 2021: 57 · 2020: 74 · 2019: 62 · 2018: 85 · 2017: 80 · 2016: 75 · 2015: 72 · 2014: 68 · 2013: 57 · 2012: 49
FWCI
50.74
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Veterans Affairs (R01 HL082480)
  • University of Michigan (UL1 RR024986)
  • National Institutes of Health (n01hr46162-13-0-1)
  • Michigan Institute for Clinical and Health Research (UL 1RR024986)
  • University of Michigan Comprehensive Cancer Center (P30 CA46952, CA46952)
  • National Heart, Lung, and Blood Institute (R01HL082480, N01HR046162, T32HL007749)
  • National Cancer Institute (P30 CA 46952)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK070875, RR024986, R01DK070875)
  • National Center for Research Resources (UL1RR024986)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
  • Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
lung microbiome, chronic obstructive pulmonary disease, healthy smokers, bronchoalveolar lavage, lung tissue sampling, bacterial community diversity, core microbiome, Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, Porphyromonas, lung transplantation
MeSH terms
Adult, Aged, Bronchoalveolar Lavage Fluid, Bronchoscopy, DNA, Bacterial, Female, Health, Humans, Lung, Male, Middle Aged, RNA, Ribosomal, 16S, Smoking, Sequence Analysis, DNA, Pulmonary Disease, Chronic Obstructive, Metagenome

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