Role of the Lung Microbiome in Health and Disease
The lung microbiome is an area of recently emerged and growing research interest. This has stemmed in part from significant advances in molecular tools to identify microbiota, such as next-generation sequencing and microarray platforms, which have facilitated new insights on the role of microbiota in organ systems outside of the lung. Thus, overarching goals of lung microbiome research include improving knowledge about microbial populations associated with the respiratory tract and lungs, their role in lung health or disease, and ultimately developing improved approaches for diagnosing and treating chronic respiratory diseases in which the microbiome has a role. However, many challenges currently exist, including clinical, technical and analytical considerations in performing such research. Strategies that help to successfully address these challenges would enable optimal realization of the above goals.
The Division of Lung Diseases (DLD) of the National Heart, Lung and Blood Institute (NHLBI) convened a workshop on December 15-16, 2011 to identify important knowledge gaps and key areas for further development to advance lung microbiome research. The workshop sought to obtain information from and facilitate discussions among investigators from diverse but relevant research expertise. Participants included clinical investigators of asthma, COPD, cystic fibrosis, and HIV, as well as basic scientists in microbiology, genomics, statistics and computational biology. Investigators involved in the ongoing NHLBI-funded Lung HIV Microbiome Project (LHMP) also contributed perspectives.
The workshop was organized into several sessions with presentations including the following areas: 1) review of current knowledge of the lung microbiome in asthma, COPD, and cystic fibrosis, 2) studies of healthy and HIV-infected individuals performed in the LHMP, 3) review of gut microbiome studies in areas such as pathogen colonization resistance and mining for immunomodulatory species, and 4) example metabolomic applications studying the gut microbiome-cardiovascular axis. In addition, open panel discussions were conducted to discuss unique lung sampling issues as well as technical and computational challenges for the field. By the conclusion of the workshop, multiple areas of need were identified and discussed. Important considerations and recommendations were compiled and are presented in this summary.
- Challenges in lung sample collection, and recognition of the potential for upper respiratory tract (URT) carryover as well as environmental sources of admixture. Given the great sensitivity of newer molecular tools for microbiota profiling, findings are subject to potential confounding from representation of organisms not necessarily derived from the lung or lower airways. Though it is possible that microbiota traditionally viewed as part of the URT also reside in the lower respiratory tract, it nonetheless is important to consider these issues when designing and performing lung microbiome studies.
- Descriptive or observational studies to continue to build knowledge and reference about the types, abundance, and distributions of microbial populations throughout the human respiratory tract. These types of studies are important for hypothesis generation, and for subsequent controlled experiments or clinical intervention studies. The resultant data also can be used to perform mechanistic experiments to determine why observed clinical associations exist. Focus on a few targeted disease populations in which viral, bacterial, and/or fungal organisms likely play a role, will initially be most useful. In this context, high quality molecular datasets of the microbiome could be obtained from leveraging existing disease study cohorts rather than development of new study cohorts.
- Investigation of viral and fungal microbial communities in the lungs, including their characterization and potential interactions with other members of the microbiome and host. Most of the focus in studies to date has been on bacterial microbiota. As specific viral and fungal species are known to cause respiratory disease, further knowledge of the viral and fungal microbiota is needed and may yield important insights.
- Development of non-invasive biomarkers of lung microbial populations. Useful methodologies would include ways to study lung microbial burden and measure relevant biomarkers of the microbiome in airway samples collected in a minimally invasive manner.
- Development of non-invasive imaging techniques, new or adapted from existing ones, to obtain reliable spatial maps of the lung microbiome. Techniques that could characterize the metabolic state of existing microorganisms in the lung microbiome would be useful.
- Investigations of functional properties of the lung microbiome to better define consequences of perturbation of microbial communities and understand what constitutes homeostasis or lack thereof. This could be pursued through generation and integration of genomic and other “-omic” data sets such as transcriptomic, metabolomic, and proteomic.
- Further research on the gut-lung axis and the potential role that gut microbial populations might play in the development of respiratory disease. This might include metabolic disturbances or autoimmune mechanisms that affect airway health.
James Beck, M.D., University of Michigan
Homer A. Boushey, M.D., University of California San Francisco
Frederic Bushman, Ph.D., University of Pennsylvania
Emily Charlson, University of Pennsylvania
Ronald Collman, M.D., Professor of Medicine
Rima Kaddurah-Daouk, Ph.D., Duke University Medical Center
Garth D. Ehrlich, Ph.D., Allegheny-Singer Research Institute
Patricia Finn, M.D., University of California San Diego
Sonia Castro Flores, M.D., University of Colorado Denver
Andrew Fontenot, M.D., University of Colorado
Mary Foulkes, Ph.D., George Washington University
Elodie Ghedin, Ph.D., University of Pittsburgh
Danial Haft, Ph.D., J. Craig Venter Institute
Laurence Huang, M.D., University of California San Francisco
Yvonne J. Huang, M.D., University of California San Francisco
Gary Huffnagle, Ph.D., University of Michigan
Kathleen Jablonski, Ph.D., George Washington University
John Lipuma, M.D., University of Michigan
Susan Lynch, Ph.D., University of California San Francisco
Fernando D. Martinez, M.D., University of Arizona
Fernando J. Martinez, M.D., University of Michigan
Alison Morris, M.D., M.S. University of Pittsburgh
Rubin Tuder, M.D., University of Colorado Denver
Robert Senior, M.D., Washington University
Homer Twigg III, M.D., Indiana University
George Weinstock, Ph.D., Washington University
Scott Weiss, M.D., M.S. Brigham and Women's Hospital
Vincent Young, M.D., University of Michigan
NHLBI and NIH Staff
Sandra Colombini-Hatch, M.D., National Heart, Lung and Blood Institute
James P. Kiley, Ph.D., National Heart, Lung and Blood Institute
Lita M. Proctor, Ph.D., National Human Genome Research Institute
Pothur Srinivas, Ph.D., MPH National Heart, Lung and Blood Institute
Hannah Peavy, M.D., National Heart, Lung and Blood Institute
Gail Weinman, M.D., National Heart, Lung and Blood Institute
Toni Punturieri, M.D., National Heart, Lung and Blood Institute
Gail Weinman, M.D., National Heart, Lung and Blood Institute
Weinu Gan Ph.D., National Heart, Lung and Blood Institute
Dorothy Gail, Ph.D., National Heart, Lung and Blood Institute
Last Updated: December 2012