title: Longitudinal analysis of the lung microbiota of cynomolgous macaques during long-term SHIV infection.
abstract: Longitudinal studies of the lung microbiome are challenging due to the invasive nature of sample collection. In addition, studies of the lung microbiome in human disease are usually performed after disease onset, limiting the ability to determine early events in the lung. We used a non-human primate model to assess lung microbiome alterations over time in response to an HIV-like immunosuppression and determined impact of the lung microbiome on development of obstructive lung disease. Cynomolgous macaques were infected with the SIV-HIV chimeric virus SHIV89.6P. Bronchoalveolar lavage fluid samples were collected pre-infection and every 4 weeks for 53 weeks post-infection. The microbiota was characterized at each time point by 16S ribosomal RNA (rRNA) sequencing.
  
  
  
  We observed individual variation in the composition of the lung microbiota with a proportion of the macaques having Tropheryma whipplei as the dominant organism in their lungs. Bacterial communities varied over time both within and between animals, but there did not appear to be a systematic alteration due to SHIV infection. Development of obstructive lung disease in the SHIV-infected animals was characterized by a relative increase in abundance of oral anaerobes. Network analysis further identified a difference in community composition that accompanied the development of obstructive disease with negative correlations between members of the obstructed and non-obstructed groups. This emphasizes how species shifts can impact multiple other species, potentially resulting in disease.
  
  
  
  This study is the first to investigate the dynamics of the lung microbiota over time and in response to immunosuppression in a non-human primate model. The persistence of oral bacteria in the lung and their association with obstruction suggest a potential role in pathogenesis. The lung microbiome in the non-human primate is a valuable tool for examining the impact of the lung microbiome in human health and disease.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.|Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Morris
authors.affiliation: Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA.|Present address: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.|Present address: Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Paulson
authors.affiliation: Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA.
authors.forename: Hisham
authors.initials: H
authors.lastname: Talukder
authors.affiliation: Department of Biology, Center for Genomics & Systems Biology and College of Global Public Health, New York University, 12 Waverly Place, New York, NY, 10003, USA.|Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Tipton
authors.affiliation: Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Kling
authors.affiliation: Tsinghua University School of Medicine, Beijing, China.
authors.forename: Lijia
authors.initials: L
authors.lastname: Cui
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Fitch
authors.affiliation: Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA.
authors.forename: Mihai
authors.initials: M
authors.lastname: Pop
authors.affiliation: Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Norris
authors.affiliation: Department of Biology, Center for Genomics & Systems Biology and College of Global Public Health, New York University, 12 Waverly Place, New York, NY, 10003, USA. elodie.ghedin@nyu.edu.|Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. elodie.ghedin@nyu.edu.
authors.forename: Elodie
authors.identifier: 0000-0002-1515-725X
authors.initials: E
authors.lastname: Ghedin
mesh_terms: D039903:Actinobacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D000818:Animals; D041963:Bacteroidetes / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology*; D000068536:Bacillota / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D045182:Fusobacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D007165:Immunosuppression Therapy; D008137:Longitudinal Studies; D008168:Lung / Q000382:microbiology; D008252:Macaca fascicularis; D064307:Microbiota / Q000235:genetics / Q000276:immunology; D020560:Proteobacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D029424:Pulmonary Disease, Chronic Obstructive / Q000382:microbiology*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D054851:Tropheryma / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*
chemical_list: D012336:RNA, Ribosomal, 16S
keywords: 16S rRNA; Microbiota; SHIV; Time series