Journal
NATURE MICROBIOLOGY
Volume 1, Issue 5, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NMICROBIOL.2016.31
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Funding
- National Institute of Allergy and Infectious Diseases (NIAID) [K23 AI102970]
- National Heart, Lung and Blood Institute (NHLBI) [R01 HL125816]
- NIAID [K24 AI080298, U01AI111598, UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]
- Clinical and Translational Science Institute (CTSI) [UL1 TR000038]
- Early Detection Research Network (EDRN) [5U01CA086137-13]
- Diane Belfer Program for Human Microbial Ecology
- Michael Saperstein Scholarship Fund
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01DK090989]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [UH2 AR57506]
- NHLBI [R01 HL090339, K24 HL123342, U01 HL098962, K24HL123342, K24 HL087713, U01-HL098957, R01-HL113252]
- NIAID
- National Cancer Institute (NCI) [UO1-AI-35042]
- General Clinical Research Center (GCRC) [5-MO1-RR-00722]
- University of California Los Angeles Clinical and Translational Research Center (UCLA CTRC) [UL1TR000124]
- National Institute of Child Health and Human Development (NICHHD) [UO1-AI-35004]
- NICHHD [UO1-HD-32632]
- Women's Interagency HIV Study (WIHS)
- NCI
- National Heart, Lung, and Blood Institute (NHLBI)
- National Institute on Deafness and Communication Disorders (NIDCD)
- Johns Hopkins University Clinical and Translational Science Awards (JHU CTSA) [UL1-TR000424]
- Eunice Kennedy Shriver NICHD
- National Institute on Drug Abuse (NIDA)
- National Institute on Mental Health (NIMH)
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Microaspiration is a common phenomenon in healthy subjects, but its frequency is increased in chronic inflammatory airway diseases, and its role in inflammatory and immune phenotypes is unclear. We have previously demonstrated that acellular bronchoalveolar lavage samples from half of the healthy people examined are enriched with oral taxa (here called pneumotype(SPT)) and this finding is associated with increased numbers of lymphocytes and neutrophils in bronchoalveolar lavage. Here, we have characterized the inflammatory phenotype using a multi-omic approach. By evaluating both upper airway and acellular bronchoalveolar lavage samples from 49 subjects from three cohorts without known pulmonary disease, we observed that pneumotype(SPT) was associated with a distinct metabolic profile, enhanced expression of inflammatory cytokines, a pro-inflammatory phenotype characterized by elevated Th-17 lymphocytes and, conversely, a blunted alveolar macrophage TLR4 response. The cellular immune responses observed in the lower airways of humans with pneumotype(SPT) indicate a role for the aspiration-derived microbiota in regulating the basal inflammatory status at the pulmonary mucosal surface.
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