Project Summary/Abstract The respiratory tract, once thought of as sterile, has now been determined to contain an active microbiome within the lung lining. The presence of a normal microbiome appears to be critical for the maintenance of a healthy lung. Disruption of the microbiome is associated with a variety of diseases including COPD, cystic fibrosis, and asthma. Environmental exposure has been shown to alter the gut microbiome and that this disruption is associated with disease. However, in the lung the effects of environmental exposure on the respiratory microbiome have not been analyzed. Ozone is a ubiquitous air pollutant that has been shown to irritate and damage the lung of both healthy and diseased individuals. It suppresses nonspecific immune function and exposes individuals to increased likelihood of respiratory infection. Ozone has been shown to damage the epithelial barrier, cause type II cell hyperplasia, and induce inflammation; its effects on the respiratory microbiome have not been analyzed. The respiratory microbiome is maintained within the ?neutral community model? by a balance between 1) immigration from the oropharynx; 2) elimination by the components of the pulmonary surface; and 3) regulation of local growth conditions within the lung lining. The immigration rate is not directly regulated but the elimination rate is dependent upon the inflammatory state while growth conditions are determined by epithelial cell function. We hypothesize that ozone disrupts the microbiome by increasing the elimination rate of microbes and altering lung lining fluid components, such that individual, potentially pathogenic, microbial species are favored in their growth. This would provide a novel mechanism whereby ozone exposure can lead to lung disease. We intend to test this hypothesis by examining the microbial ecology following ozone exposure, which we predict will be disrupted and reduced in diversity. Further, we will directly examine the ability of microbes to grow on the constituent parts of the lung lining fluid and examine how ozone exposure alters these effects. Finally, we will use two strains of mice in which the inflammatory response to ozone is altered, namely Sftpd-/- and NOS2-/-, to determine how altered ozone responsiveness changes the effects on the microbiome. These studies will examine the mechanisms involved in controlling the microbial ecology of the respiratory compartment and elucidate the role of these mechanisms in the host response to ozone exposure.
|Effective start/end date||9/15/18 → 8/31/21|
- National Institute of Environmental Health Sciences: $193,750.00
- National Institute of Environmental Health Sciences: $232,500.00
- Pulmonary and Respiratory Medicine
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