Editors' ChoiceCOPD

Unwanted guests: Bacterial microbiome in COPD

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Science Translational Medicine  25 May 2016:
Vol. 8, Issue 340, pp. 340ec82
DOI: 10.1126/scitranslmed.aaf9195

COPD is the third leading cause of death in the United States. A major component of its natural history is ongoing inflammatory injury despite smoking cessation. Differences have been reported in the respiratory microbiome of COPD patients compared with healthy individuals, and thus it is possible that the lung bacterial microbiome plays a role in this persistent inflammation.

Yadava et al. used repetitive airway instillation of LPS and elastase in mice to reproduce essential features of COPD, including decreased lung function, emphysema, and inflammation. Analysis of the lung microbiome revealed decreased bacterial richness and diversity in LPS/elastase-treated mice compared with control, with predominance of three genera, two of which have been reported to be present in the lung microbiome of clinical COPD. Antibiotic treatment of the LPS/elastase model decreased bacterial burden by several orders of magnitude and markedly diminished physiologic and inflammatory indices, including respiratory immunoglobulins reactive to lung autoantigens collagen and elastase and the number of neutrophils and IL-17A+ CD4 T cells in lung lavage fluid.

To look at the effects of the altered microbiota, mice pretreated with antibiotics were instilled with lavage fluid recovered from either LPS/elastase-treated or PBS-treated mice, in addition to LPS/elastase. Mice that were instilled with lavage fluid from LPS/elastase-treated mice had increased IL-17A+ CD4 T cells in their lavage fluid compared with PBS-lavage–treated controls. Underscoring a pathogenic role for IL-17A–mediated inflammation, IL-17A antibody blockade blunted physiologic and inflammatory parameters in the LPS/elastase COPD model. Taken together, these provocative data in a murine model implicate the lung bacterial microbiome in the development of IL-17A–mediated inflammation and COPD. Future studies should seek to replicate these results in other preclinical COPD models and with alternative approaches to genus-specific experimental manipulation of the microbiome, an approach that could eventually have relevance to treatment of patients with COPD.

K. Yadava et al., Microbiota promotes chronic pulmonary inflammation by enhancing IL-17A and autoantibodies. Am. J. Respir. Crit. Care. Med. 193, 975–987 (2016) [Abstract]

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