# Functional Analysis of the Pulmonary Microbiome during COPD

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $654,446

## Abstract

Summary
Bacterial colonization/infection is ubiquitous in Chronic Obstructive Pulmonary Disease (COPD) patients and
has been felt to be biologically relevant in disease. The quantity of airway mucus can be altered in COPD and
contribute to chronic and acute airway obstruction, symptoms of chronic bronchitis and bacterial colonization.
Correlations have been reported between the identification of bacteria and the intensity of the
inflammatory/immune response, increased cough and sputum and increased rates of acute exacerbations of
COPD. It is now appreciated that the COPD lung harbors a microbiome, distinct from that in healthy
individuals, which is not captured by standard culture techniques. Unlike studies of the gastrointestinal tract,
culture-independent analyses of the airways have not identified significant numbers of routinely unculturable
bacteria. Rather, these studies implicate the existence of culturable bacterial species, such as Pseudomonas
spp. that may go through cycles of culturability and "unculturability" during disease. These likely reflect
changes in the nutritional environment of the lungs, adaptation to host defenses and changes in the metabolic
activity of the bacteria. More recently, studies have begun to support the concept that host-derived factors
during inflammation may be a driving force for adaptation and metabolic shifts in many respiratory bacteria.
Our hypothesis in this proposal is that the inflammatory response (i.e. IL-17 driven inflammation, interferon
(IFN)-mediated inducible nitric oxide synthase (iNOS) induction and activation of catecholamine-producing
inflammatory macrophages) may also drive Pseudomonas infection, creating a self-reinforcing cycle of
inflammation. P. aeruginosa has long been held to be an obligate aerobic bacterium; however, recent studies
have highlighted that this is not true, providing a bacteriologic mechanism for its growth in mucus-rich regions
of diseased lungs in the presence of ongoing inflammation. In support of this hypothesis, inflammatory
macrophages can produce reactive nitrogen species and catecholamines, both of which have the potential to
directly promote Pseudomonas colonization and virulence. In turn, this activates airway epithelial pathways
involved in mucus over-production in the airways that, altogether, perpetuate airway disease by creating
nitrate-rich micro-aerophilic or anaerobic niches that promote Pseudomonas colonization.

## Key facts

- **NIH application ID:** 9847995
- **Project number:** 5R01HL121774-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Gary B Huffnagle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $654,446
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9847995

## Citation

> US National Institutes of Health, RePORTER application 9847995, Functional Analysis of the Pulmonary Microbiome during COPD (5R01HL121774-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9847995. Licensed CC0.

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