# The role of the lung microbiome in oxygen-induced lung injury

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $415,715

## Abstract

PROJECT SUMMARY/ABSTRACT
Background and long-term objectives: This proposed research will advance our understanding of how the
lung microbiome contributes to the pathogenesis and perpetuation of oxygen-induced lung injury. Inhaled
oxygen is among our most commonly administered therapies. Yet hyperoxia - elevated inspired oxygen -
causes lethal lung injury in animals, and in humans is associated with increased mortality and development of
the acute respiratory distress syndrome. We have recently discovered that hyperoxia acutely alters lung
microbiota. This oxygen-induced dysbiosis is strongly and temporally correlated with alveolar inflammation. We
have discovered that germ-free mice - experimental mice devoid of microbiota - are protected from oxygen-
induced lung injury, an observation that cannot be explained via our conventional model of oxygen-induced
lung injury. Conversely, lung injury alters lung microbiota by changing bacterial growth conditions within the
lung microenvironment. We have discovered that germ-free mice are protected from non-resolving lung injury
(bleomycin), indicating that the microbiome is necessary for perpetuation of lung injury. The discovery of the
lung microbiome has thus broadened our model of pathogenesis. The mechanisms by which lung microbiota
mediate oxygen-induced lung injury, and are in turn altered by lung injury, are undetermined.
The central hypothesis of this proposal is that specific bacteria within the lung ecosystem propel alveolar
inflammation in oxygen-induced lung injury, and these bacteria are enriched within the lung microbiome both
by hyperoxia itself and by the altered ecology of injured lungs. The rationale is that these discoveries will
facilitate the development of therapies for the prevention and treatment of oxygen-related human lung disease.
Specific Aim 1: To determine the microbial and molecular pathways by which oxygen therapy alters
lung microbiota, mediating host inflammation and injury. We will accomplish this Aim by integrating
complementary experimental approaches: in vivo heterogeneity analysis of host-microbiome interactions in
mice; in vivo germ-free, gnotobiotic, and antibiotic-treated hyperoxia modeling in mice; data science
interrogation of observational human data using a validated machine-learning algorithm.
Specific Aim 2: To determine the molecular pathways by which oxygen-induced host inflammation and
injury alter lung microbiota, perpetuating respiratory dysbiosis and lung injury. We will accomplish this
Aim by integrating complementary experimental approaches: a novel ex vivo culture assay that identifies host-
derived mediators of bacterial growth; in vivo augmentation and inhibition of the host response in hyperoxia.
This translational research approach will determine 1) the key members of the lung microbiome that mediate
oxygen-induced lung injury, 2) the pathways by which these bacteria promote alveolar inflammation, and 3) the
ecologic factors within the injured ...

## Key facts

- **NIH application ID:** 9893017
- **Project number:** 5R01HL144599-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Robert Pickett Dickson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $415,715
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893017

## Citation

> US National Institutes of Health, RePORTER application 9893017, The role of the lung microbiome in oxygen-induced lung injury (5R01HL144599-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9893017. Licensed CC0.

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