Bacteria are prevalent throughout the human body, residing at all interfaces with the external environment. These microbes, which outnumber human cells ten to one, are highly physiologically active and known to influence the health of their host. Although most studies to date have focused on microbes of the skin, oropharynx, gastrointestinal tract, and vagina, there is now an understanding that the lungs are not sterile, as was once believed. In fact, evidence shows that microbial burden and diversity in the lungs differs between healthy individuals and those with lung disease. Additionally, microbial composition in the lungs has been linked to respiratory disease severity. Since it is known that microbial communities in the gut can metabolize environmental toxicants, stimulate host inflammatory response, and increase risk of host infection, it is likely that respiratory microbes also play an important role in human health. A major challenge to researching the respiratory microbiome is the lack of a well-established, non-invasive measure in the lungs. Bronchoalveolar lavage is the most direct approach to measure the lungs, but it is an invasive procedure performed under sedation at the hospital. This makes it too burdensome on participants and cost-prohibitive for large clinical and epidemiology studies. To overcome these limitations, the aim of this exploratory study is to systematically investigate exhaled breath condensate as a novel, non-invasive medium to characterize the respiratory microbiome. Because exhaled breath condensate may reflect several inter-connected biological compartments, we plan to characterize the microbial communities of concurrent samples of exhaled breath condensate, bronchoalveolar lavage fluid, oral wash, nasal swab, fecal, and inspired air samples collected from 18 healthy individuals. Specifically we plan to: 1) assess how well the microbial communities in exhaled breath condensate reflect the microbial communities in the lungs and 2) identify the origins (mouth, nose, gut, inspired air) of any microbial communities in exhaled breath condensate not present in the lungs. The ability to characterize the lung microbiome using exhaled breath condensate, alone or paired with other non-invasive samples will open the door to large-scale population-based epidemiology studies that are currently cost-prohibitive and logistically infeasible. We plan to follow this work with future studies of the respiratory microbiome's role in processing inhaled environmental pollutants, predicting survival among patients with severe lung disease, and as a diagnostic for clinical use. Thus, this work is expected to lead to substantial improvements in our understanding of the role of the respiratory microbiome on human health.

Public Health Relevance

Microbes live throughout the human body, outnumbering human cells ten to one. While these microbes are highly biologically active and have been linked with disease, identifying microbes in the lungs currently requires a procedure at the hospital performed under sedation. By proposing a new method that can be performed without sedation, this research may substantially improve our ability to study the role of microbes on lung health in the general population as well as reduce the burden and costs to patients at high risk for lung infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI117371-02
Application #
9228922
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Dong, Gang
Project Start
2016-02-18
Project End
2018-01-31
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
2
Fiscal Year
2017
Total Cost
$193,750
Indirect Cost
$68,750
Name
University of Michigan Ann Arbor
Department
Type
Schools of Public Health
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Curtis, Jeffrey L (2017) A Hairline Crack in the Levee: Focal Secretory IgA Deficiency as a First Step toward Emphysema. Am J Respir Crit Care Med 195:970-973
Adar, Sara D; Huffnagle, Gary B; Curtis, Jeffrey L (2016) The respiratory microbiome: an underappreciated player in the human response to inhaled pollutants? Ann Epidemiol 26:355-9