Background: Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection. Methods: Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy. Lung specimens were not contaminated with upper airway taxa since they were obtained surgically. The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing. Data analyses were performed using QIIME, SourceTracker, and R. Results: Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways. Each subject's own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites. Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject. SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown. An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue. Conclusion: This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples. In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that aspiration is a source of the COPD lung microbiota.
Bibliographical noteFunding Information:
The authors thank Richard Haupert for the assistance with qPCR analyses and figure and table preparation; Shane Hodgson for the assistance with figure preparation; Etian Podgaetz, MD, Anne Steckler, RN, and Cheryl Davenport, NP, for the assistance with recruitment and sampling; and Susan Johnson, Angela Fabbrini, and Miranda Deconcini for the assistance with recruitment and IRB submissions. This work was supported in part by 5KL2TR113 and the NIH Clinical and Translational Science Award at the University of Minnesota, 8UL1TR000114 (A.A.P.); NIAID/NIH 5T32AI055433 (A.A.P); Career Development Award 1IK2CX001095 (A.A.P.) from the United states (U.S.) Department of Veterans Affairs Clinical Sciences Research and Development Service; the American Lung Association (ALA) Biomedical Research Grant 348261 (A.A.P.); and the Minnesota Veterans Medical Research and Education Foundation (C.H.W.). The study sponsors did not play a role in the study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. The corresponding author confirms that she had full access to all the data in the study and had final responsibility for the decision to submit for publication.
- Chronic obstructive
- Emigration and immigration
- Pulmonary disease