The Role of the Lung Microbiome in Oxygen-Induced Lung Injury
Revealing how oxygen alters lung bacteria, contributing to lethal lung injury.
Project at a Glance
Product Type:
Therapeutic
Project Start Date:
July 1, 2019
Principal Investigators:
Robert Dickson, MD
Solution Sheet:
Download Solution Sheet (PDF)
Funding History:
$2,006,663 in non-dilutive funding • 2019 $2,006,663 NHLBI • Substantial additional departmental, school and center based support
Overview
• To determine the microbial and molecular pathways by which oxygen therapy alters lung microbiota, mediating host inflammation and injury.
• To determine the molecular pathways by which oxygen-induced host inflammation and injury alter lung microbiota, perpetuating respiratory dysbiosis and lung injury.
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
3. The ecologic factors within the injured lung environment that promote their growth
Significant Need
Inhaled oxygen is among the most common medical therapies administered. Yet hyperoxia—elevated inspired oxygen—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.
Competitive Advantage
These discoveries will facilitate the development of therapies for the prevention and treatment of oxygen-related human lung disease.
• Generates critical new information
• Improves patient outcomes
• Facilitates development of new treatments
Funding Organization(s)
