title: Immune Response and Mortality Risk Relate to Distinct Lung Microbiomes in Patients with HIV and Pneumonia.
abstract: The potential role of the airway microbiota in dictating immune responses and infection outcomes in HIV-associated pneumonia is largely unknown.
  
  
  
  To investigate whether microbiologically and immunologically distinct subsets of patients with HIV and pneumonia exist and are related to mortality.
  
  
  
  Bronchoalveolar lavage samples from Ugandan patients with HIV and pneumonia (n = 182) were obtained at study enrollment (following antibiotic treatment); patient demographics including 8- and 70-day mortality were collected. Lower airway bacterial community composition was assessed via amplification and sequencing of the V4 region of the 16S ribosomal RNA gene. Host immune response gene expression profiles were generated by quantitative polymerase chain reaction using RNA extracted from bronchoalveolar lavage fluid. Liquid and gas chromatography mass spectrometry was used to profile serum metabolites.
  
  
  
  Based on airway microbiome composition, most patients segregated into three distinct groups, each of which were predicted to encode metagenomes capable of producing metabolites characteristically enriched in paired serum samples from these patients. These three groups also exhibited differences in mortality; those with the highest rate had increased ceftriaxone administration and culturable Aspergillus, and demonstrated significantly increased induction of airway T-helper cell type 2 responses. The group with the lowest mortality was characterized by increased expression of T-cell immunoglobulin and mucin domain 3, which down-regulates T-helper cell type 1 proinflammatory responses and is associated with chronic viral infection.
  
  
  
  These data provide evidence that compositionally and structurally distinct lower airway microbiomes are associated with discrete local host immune responses, peripheral metabolic reprogramming, and different rates of mortality.
authors.affiliation: 1 Division of Gastroenterology, Department of Medicine.|2 Biomedical Sciences Graduate Program.
authors.forename: Meera K
authors.initials: MK
authors.lastname: Shenoy
authors.affiliation: 1 Division of Gastroenterology, Department of Medicine.
authors.forename: Shoko
authors.initials: S
authors.lastname: Iwai
authors.affiliation: 1 Division of Gastroenterology, Department of Medicine.
authors.forename: Din L
authors.initials: DL
authors.lastname: Lin
authors.affiliation: 3 Infectious Diseases Research Collaboration, Mulago Hospital, Makerere University, Kampala, Uganda.
authors.forename: William
authors.initials: W
authors.lastname: Worodria
authors.affiliation: 3 Infectious Diseases Research Collaboration, Mulago Hospital, Makerere University, Kampala, Uganda.
authors.forename: Irene
authors.initials: I
authors.lastname: Ayakaka
authors.affiliation: 3 Infectious Diseases Research Collaboration, Mulago Hospital, Makerere University, Kampala, Uganda.
authors.forename: Patrick
authors.initials: P
authors.lastname: Byanyima
authors.affiliation: 3 Infectious Diseases Research Collaboration, Mulago Hospital, Makerere University, Kampala, Uganda.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kaswabuli
authors.affiliation: 4 HIV, Infectious Diseases and Global Medicine Division, San Francisco General Hospital.
authors.forename: Serena
authors.initials: S
authors.lastname: Fong
authors.affiliation: 4 HIV, Infectious Diseases and Global Medicine Division, San Francisco General Hospital.
authors.forename: Stephen
authors.initials: S
authors.lastname: Stone
authors.affiliation: 4 HIV, Infectious Diseases and Global Medicine Division, San Francisco General Hospital.|5 Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, and.
authors.forename: Emily
authors.initials: E
authors.lastname: Chang
authors.affiliation: 6 Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut; and.|7 Pulmonary, Critical Care, and Sleep Medicine Section, Yale School of Medicine, New Haven, Connecticut.
authors.forename: J Lucian
authors.initials: JL
authors.lastname: Davis
authors.affiliation: 1 Division of Gastroenterology, Department of Medicine.
authors.forename: Ali Ahmad
authors.initials: AA
authors.lastname: Faruqi
authors.affiliation: 8 Division of Biostatistics, University of California San Francisco, San Francisco, California.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Segal
authors.affiliation: 4 HIV, Infectious Diseases and Global Medicine Division, San Francisco General Hospital.|5 Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, and.
authors.forename: Laurence
authors.initials: L
authors.lastname: Huang
authors.affiliation: 1 Division of Gastroenterology, Department of Medicine.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Lynch
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D060085:Coinfection / Q000276:immunology / Q000382:microbiology / Q000401:mortality*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000382:microbiology / Q000401:mortality*; D006801:Humans; D008168:Lung / Q000382:microbiology*; D008297:Male; D064307:Microbiota / Q000235:genetics / Q000276:immunology*; D018410:Pneumonia, Bacterial / Q000150:complications / Q000276:immunology / Q000401:mortality*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012307:Risk Factors
chemical_list: D012336:RNA, Ribosomal, 16S
keywords: HIV; immune response; microbiota; mortality; pneumonia