title: Correlation of the lung microbiota with metabolic profiles in bronchoalveolar lavage fluid in HIV infection.
abstract: BACKGROUND
  While 16S ribosomal RNA (rRNA) sequencing has been used to characterize the lung's bacterial microbiota in human immunodeficiency virus (HIV)-infected individuals, taxonomic studies provide limited information on bacterial function and impact on the host. Metabolic profiles can provide functional information on host-microbe interactions in the lungs. We investigated the relationship between the respiratory microbiota and metabolic profiles in the bronchoalveolar lavage fluid of HIV-infected and HIV-uninfected outpatients.
  
  
  RESULTS
  Targeted sequencing of the 16S rRNA gene was used to analyze the bacterial community structure and liquid chromatography-high-resolution mass spectrometry was used to detect features in bronchoalveolar lavage fluid. Global integration of all metabolic features with microbial species was done using sparse partial least squares regression. Thirty-nine HIV-infected subjects and 20 HIV-uninfected controls without acute respiratory symptoms were enrolled. Twelve mass-to-charge ratio (m/z) features from C18 analysis were significantly different between HIV-infected individuals and controls (false discovery rate (FDR) = 0.2); another 79 features were identified by network analysis. Further metabolite analysis demonstrated that four features were significantly overrepresented in the bronchoalveolar lavage (BAL) fluid of HIV-infected individuals compared to HIV-uninfected, including cystine, two complex carbohydrates, and 3,5-dibromo-L-tyrosine. There were 231 m/z features significantly associated with peripheral blood CD4 cell counts identified using sparse partial least squares regression (sPLS) at a variable importance on projection (VIP) threshold of 2. Twenty-five percent of these 91 m/z features were associated with various microbial species. Bacteria from families Caulobacteraceae, Staphylococcaceae, Nocardioidaceae, and genus Streptococcus were associated with the greatest number of features. Glycerophospholipid and lineolate pathways correlated with these bacteria.
  
  
  CONCLUSIONS
  In bronchoalveolar lavage fluid, specific metabolic profiles correlated with bacterial organisms known to play a role in the pathogenesis of pneumonia in HIV-infected individuals. These findings suggest that microbial communities and their interactions with the host may have functional metabolic impact in the lung.
authors.affiliation: Pulmonary Medicine, Department of Veterans Affairs Medical Center, 1670 Clairmont Rd, Mailstop 151p, Decatur, 30033, GA, USA. skomaku@emory.edu.|Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University, Atlanta, GA, USA. skomaku@emory.edu.
authors.forename: Sushma K
authors.initials: SK
authors.lastname: Cribbs
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University, Atlanta, GA, USA. kuppal2@emory.edu.
authors.forename: Karan
authors.initials: K
authors.lastname: Uppal
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University, Atlanta, GA, USA. sli49@emory.edu.
authors.forename: Shuzhao
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University, Atlanta, GA, USA. dpjones@emory.edu.
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.affiliation: Department of Medicine, HIV/AIDS Division and Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, Medicine, San Francisco, CA, USA. laurence.huang@ucsf.edu.
authors.forename: Laurence
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. tipton.laura@gmail.com.|Department of Biology, Center for Genomics and Systems Biology, and Global Institute of Public Health, New York University, New York, NY, USA. tipton.laura@gmail.com.
authors.forename: Laura
authors.initials: L
authors.lastname: Tipton
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. fitchad@pitt.edu.
authors.forename: Adam
authors.initials: A
authors.lastname: Fitch
authors.affiliation: Department of Clinical Pharmacy, University of California, San Francisco, Medicine, San Francisco, CA, USA. ruth.greenblatt@ucsf.edu.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Greenblatt
authors.affiliation: Departments of Infectious Diseases and Microbiology and Epidemiology, GSPH, University of Pittsburgh, Pittsburgh, PA, USA. kingsley@pitt.edu.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Kingsley
authors.affiliation: Pulmonary Medicine, Department of Veterans Affairs Medical Center, 1670 Clairmont Rd, Mailstop 151p, Decatur, 30033, GA, USA. dguidot@emory.edu.|Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University, Atlanta, GA, USA. dguidot@emory.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Guidot
authors.affiliation: Department of Biology, Center for Genomics and Systems Biology, and Global Institute of Public Health, New York University, New York, NY, USA. elodie.ghedin@nyu.edu.
authors.forename: Elodie
authors.initials: E
authors.lastname: Ghedin
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. morrisa@upmc.edu.
authors.forename: Alison
authors.initials: A
authors.lastname: Morris
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D016022:Case-Control Studies; D042063:Caulobacteraceae / Q000145:classification / Q000235:genetics / Q000378:metabolism; D002853:Chromatography, Liquid; D003553:Cystine / Q000378:metabolism; D005260:Female; D020404:Glycerophospholipids / Q000378:metabolism; D006678:HIV / Q000254:growth & development; D015658:HIV Infections / Q000378:metabolism* / Q000382:microbiology* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D016018:Least-Squares Analysis; D008168:Lung / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome; D064307:Microbiota / Q000235:genetics*; D009618:Nocardiaceae / Q000145:classification / Q000235:genetics / Q000378:metabolism; D012336:RNA, Ribosomal, 16S / Q000235:genetics* / Q000378:metabolism; D017423:Sequence Analysis, RNA; D040141:Staphylococcaceae / Q000145:classification / Q000235:genetics / Q000378:metabolism; D013291:Streptococcus / Q000145:classification / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D020404:Glycerophospholipids; D012336:RNA, Ribosomal, 16S; D014443:Tyrosine; D003553:Cystine; C082610:3,5-dibromotyrosine