Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype

• Published in: Nature microbiology Vol. 1; no. 5; p. 16031
• Main Authors: Segal, Leopoldo N., Clemente, Jose C., Tsay, Jun-Chieh J., Koralov, Sergei B., Keller, Brian C., Wu, Benjamin G., Li, Yonghua, Shen, Nan, Ghedin, Elodie, Morris, Alison, Diaz, Phillip, Huang, Laurence, Wikoff, William R., Ubeda, Carles, Artacho, Alejandro, Rom, William N., Sterman, Daniel H., Collman, Ronald G., Blaser, Martin J., Weiden, Michael D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.04.2016; Nature Publishing Group
• Subjects: 631/326/2565/2134; 692/308/575; 692/4017; Alveoli; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - microbiology; Bronchus; Cytokines; Genotype & phenotype; Helper cells; Humans; Immune response; Immune response (cell-mediated); Infectious Diseases; Leukocytes (neutrophilic); Life Sciences; Lung diseases; Lymphocytes; Lymphocytes T; Macrophages; Medical Microbiology; Microbiology; Microbiomes; Microbiota; Mucosa; Parasitology; Phenotypes; Pneumonia - microbiology; Pneumonia - pathology; Respiratory Aspiration - complications; Respiratory tract diseases; Th17 Cells - immunology; TLR4 protein; Toll-like receptors; Virology
• ISSN: 2058-5276; 2058-5276
• DOI: 10.1038/nmicrobiol.2016.31

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. Enrichment of oral microbiota in the bronchoalveolar lavage of apparently healthy people is associated with a pro-inflammatory phenotype, suggesting that aspiration-derived microbiota play a role in regulating basal inflammatory status.