title: Gut Microbiota Predict Pulmonary Infiltrates after Allogeneic Hematopoietic Cell Transplantation.
abstract: Pulmonary complications (PCs) cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HCT). Shifts in gut microbiota have been linked to HCT outcomes; however, their effect on PCs is unknown.
  
  
  
  To investigate whether changes in gut microbiota are associated with PCs after HCT.
  
  
  
  A single-center observational study was performed on 94 patients who underwent HCT from 2009 to 2011 and who were previously enrolled in a protocol for 16S ribosomal RNA sequencing of fecal microbiota. The primary endpoint, PC, was defined by new abnormal parenchymal findings on chest imaging in the setting of respiratory signs and/or symptoms. Outcomes were collected up to 40 months after transplant. Clinical and microbiota risk factors for PCs and mortality were evaluated using survival analysis.
  
  
  
  One hundred twelve PCs occurred in 66 (70.2%) subjects. A high comorbidity index (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.30-4.00; P = 0.004), fluoroquinolones (HR, 2.29, 95% CI, 1.32-3.98; P = 0.003), low baseline diversity (HR, 2.63; 95% CI, 1.22-5.32; P = 0.015), and γ-proteobacteria domination of fecal microbiota (HR, 2.64; 95% CI, 1.10-5.65; P = 0.031), which included common respiratory pathogens, predicted PCs. In separate analyses, low baseline diversity was associated with PCs that occurred preengraftment (HR, 6.30; 95% CI, 1.42-31.80; P = 0.016), whereas γ-proteobacteria domination predicted PCs postengraftment (HR, 3.68; 95% CI, 1.49-8.21; P = 0.006) and overall mortality (HR, 3.52; 95% CI, 1.28-9.21; P = 0.016). Postengraftment PCs were also independent predictors of death (HR, 2.50; 95% CI, 1.25-5.22; P = 0.009).
  
  
  
  This is the first study to demonstrate prospective changes in gut microbiota associated with PCs after HCT. Postengraftment PCs and γ-proteobacteria domination were predictive of mortality. This suggests an adverse relationship between the graft and lung, which is perhaps mediated by bacterial composition in the gut. Further study is warranted.
authors.affiliation: 1 Pulmonary Service.
authors.forename: Bianca
authors.initials: B
authors.lastname: Harris
authors.affiliation: 2 Infectious Diseases Service, and.
authors.forename: Sejal M
authors.initials: SM
authors.lastname: Morjaria
authors.affiliation: 3 Lucille Castori Center for Microbes, Inflammation and Cancer, Sloan Kettering Institute, New York, New York; and.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Littmann
authors.affiliation: 1 Pulmonary Service.|4 Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Geyer
authors.affiliation: 1 Pulmonary Service.|4 Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Diane E
authors.initials: DE
authors.lastname: Stover
authors.affiliation: 5 Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.|4 Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Juliet N
authors.initials: JN
authors.lastname: Barker
authors.affiliation: 5 Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.|4 Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Giralt
authors.affiliation: 2 Infectious Diseases Service, and.|4 Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Ying
authors.initials: Y
authors.lastname: Taur
authors.affiliation: 2 Infectious Diseases Service, and.|3 Lucille Castori Center for Microbes, Inflammation and Cancer, Sloan Kettering Institute, New York, New York; and.|4 Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
mesh_terms: D000328:Adult; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008171:Lung Diseases / Q000209:etiology* / Q000382:microbiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000401:mortality
keywords: microbiota; pulmonary disease; stem cell transplantation