title: The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation.
abstract: Highly diverse bacterial populations inhabit the gastrointestinal tract and modulate host inflammation and promote immune tolerance. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), the gastrointestinal mucosa is damaged, and colonizing bacteria are impacted, leading to an impaired intestinal microbiota with reduced diversity. We examined the impact of intestinal diversity on subsequent mortality outcomes following transplantation. Fecal specimens were collected from 80 recipients of allo-HSCT at the time of stem cell engraftment. Bacterial 16S rRNA gene sequences were characterized, and microbial diversity was estimated using the inverse Simpson index. Subjects were classified into high, intermediate, and low diversity groups and assessed for differences in outcomes. Mortality outcomes were significantly worse in patients with lower intestinal diversity; overall survival at 3 years was 36%, 60%, and 67% for low, intermediate, and high diversity groups, respectively (P = .019, log-rank test). Low diversity showed a strong effect on mortality after multivariate adjustment for other clinical predictors (transplant related mortality: adjusted hazard ratio, 5.25; P = .014). In conclusion, the diversity of the intestinal microbiota at engraftment is an independent predictor of mortality in allo-HSCT recipients. These results indicate that the intestinal microbiota may be an important factor in the success or failure in allo-HSCT.
authors.affiliation: Infectious Disease Service, Department of Medicine, and Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan-Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY;
authors.forename: Ying
authors.initials: Y
authors.lastname: Taur
authors.affiliation: Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan-Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; and.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Jenq
authors.affiliation: Weill Cornell Medical College, New York, NY; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; and.
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Perales
authors.affiliation: Infectious Disease Service, Department of Medicine, and.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Littmann
authors.affiliation: Infectious Disease Service, Department of Medicine, and.
authors.forename: Sejal
authors.initials: S
authors.lastname: Morjaria
authors.affiliation: Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan-Kettering Cancer Center, New York, NY;
authors.forename: Lilan
authors.initials: L
authors.lastname: Ling
authors.affiliation: Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan-Kettering Cancer Center, New York, NY;
authors.forename: Daniel
authors.initials: D
authors.lastname: No
authors.affiliation: Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan-Kettering Cancer Center, New York, NY;
authors.forename: Asia
authors.initials: A
authors.lastname: Gobourne
authors.affiliation: Genomics Core Laboratory and.
authors.forename: Agnes
authors.initials: A
authors.lastname: Viale
authors.affiliation: Weill Cornell Medical College, New York, NY; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; and.
authors.forename: Parastoo B
authors.initials: PB
authors.lastname: Dahi
authors.affiliation: Weill Cornell Medical College, New York, NY; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; and.
authors.forename: Doris M
authors.initials: DM
authors.lastname: Ponce
authors.affiliation: Weill Cornell Medical College, New York, NY; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; and.
authors.forename: Juliet N
authors.initials: JN
authors.lastname: Barker
authors.affiliation: Weill Cornell Medical College, New York, NY; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; and.
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
authors.affiliation: Weill Cornell Medical College, New York, NY; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; and Immunology Program, Sloan-Kettering Institute, New York, NY.
authors.forename: Marcel
authors.initials: M
authors.lastname: van den Brink
authors.affiliation: Infectious Disease Service, Department of Medicine, and Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan-Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY; Immunology Program, Sloan-Kettering Institute, New York, NY.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
mesh_terms: D000328:Adult; D001419:Bacteria / Q000145:classification / Q000235:genetics; D005243:Feces / Q000382:microbiology; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D014644:Genetic Variation; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D064307:Microbiota / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D010802:Phylogeny; D011379:Prognosis; D016016:Proportional Hazards Models; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D015996:Survival Rate; D014184:Transplantation, Homologous
chemical_list: D012336:RNA, Ribosomal, 16S