title: Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype.
abstract: 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 pneumotypeSPT) 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 pneumotypeSPT 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 pneumotypeSPT indicate a role for the aspiration-derived microbiota in regulating the basal inflammatory status at the pulmonary mucosal surface.
authors: Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, USA.|Department of Medicine, New York University School of Medicine, New York, New York, USA.
authors: Leopoldo N
authors: LN
authors: Segal
authors: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.|Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
authors: Jose C
authors: http://orcid.org/0000-0002-3970-9856
authors: JC
authors: Clemente
authors: Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, USA.|Department of Medicine, New York University School of Medicine, New York, New York, USA.
authors: Jun-Chieh J
authors: http://orcid.org/0000-0002-2282-2510
authors: JC
authors: Tsay
authors: Department of Pathology, New York University School of Medicine, New York, New York, USA.
authors: Sergei B
authors: SB
authors: Koralov
authors: Division of Pulmonary and Critical Care Medicine, The Ohio State University, Columbus, Ohio, USA.
authors: Brian C
authors: BC
authors: Keller
authors: Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, USA.|Department of Medicine, New York University School of Medicine, New York, New York, USA.
authors: Benjamin G
authors: BG
authors: Wu
authors: Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, USA.|Department of Medicine, New York University School of Medicine, New York, New York, USA.
authors: Yonghua
authors: Y
authors: Li
authors: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.
authors: Nan
authors: N
authors: Shen
authors: Department of Biology, Center for Genomics &Systems Biology, College of Global Public Health, New York University, New York, New York, USA.
authors: Elodie
authors: E
authors: Ghedin
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pennsylvania, USA.
authors: Alison
authors: A
authors: Morris
authors: Division of Pulmonary and Critical Care Medicine, The Ohio State University, Columbus, Ohio, USA.
authors: Phillip
authors: P
authors: Diaz
authors: Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors: Laurence
authors: L
authors: Huang
authors: Department of Molecular and Cellular Biology &Genome Center, University of California, Davis, California, USA.
authors: William R
authors: WR
authors: Wikoff
authors: Center for Public Health Research, FISABIO, Valencia, Spain.
authors: Carles
authors: C
authors: Ubeda
authors: Center for Public Health Research, FISABIO, Valencia, Spain.
authors: Alejandro
authors: A
authors: Artacho
authors: Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, USA.|Department of Medicine, New York University School of Medicine, New York, New York, USA.
authors: William N
authors: WN
authors: Rom
authors: Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, USA.|Department of Medicine, New York University School of Medicine, New York, New York, USA.
authors: Daniel H
authors: DH
authors: Sterman
authors: Department of Medicine and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Ronald G
authors: RG
authors: Collman
authors: Department of Medicine, New York University School of Medicine, New York, New York, USA.
authors: Martin J
authors: MJ
authors: Blaser
authors: Division of Pulmonary, Critical Care and Sleep Medicine, New York University School of Medicine, New York, USA.|Department of Medicine, New York University School of Medicine, New York, New York, USA.
authors: Michael D
authors: MD
authors: Weiden
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000382:microbiology; D006801:Humans; D064307:Microbiota; D011014:Pneumonia / Q000382:microbiology* / Q000473:pathology*; D053120:Respiratory Aspiration / Q000150:complications*; D058504:Th17 Cells / Q000276:immunology*