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Infect Immun. 2019 Aug 21;87(9). pii: e00206-19. doi: 10.1128/IAI.00206-19. Print 2019 Sep.

Antibiotic-Induced Shifts in Fecal Microbiota Density and Composition during Hematopoietic Stem Cell Transplantation.

Author information

1
Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering, New York, New York, USA.
2
Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering, New York, New York, USA.
3
Weill Cornell Medical College, New York, New York, USA.
4
Computational Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering, New York, New York, USA.
5
Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering, New York, New York, USA.
6
Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering, New York, New York, USA.
7
Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering, New York, New York, USA taury@mskcc.org.
#
Contributed equally

Abstract

Dramatic microbiota changes and loss of commensal anaerobic bacteria are associated with adverse outcomes in hematopoietic cell transplantation (HCT) recipients. In this study, we demonstrate these dynamic changes at high resolution through daily stool sampling and assess the impact of individual antibiotics on those changes. We collected 272 longitudinal stool samples (with mostly daily frequency) from 18 patients undergoing HCT and determined their composition by multiparallel 16S rRNA gene sequencing as well as the density of bacteria in stool by quantitative PCR (qPCR). We calculated microbiota volatility to quantify rapid shifts and developed a new dynamic systems inference method to assess the specific impact of antibiotics. The greatest shifts in microbiota composition occurred between stem cell infusion and reconstitution of healthy immune cells. Piperacillin-tazobactam caused the most severe declines among obligate anaerobes. Our approach of daily sampling, bacterial density determination, and dynamic systems modeling allowed us to infer the independent effects of specific antibiotics on the microbiota of HCT patients.

KEYWORDS:

antibiotics; commensal anaerobes; hematopoietic cell transplantation; microbiome; systems biology

PMID:
31262981
PMCID:
PMC6704593
DOI:
10.1128/IAI.00206-19
[Indexed for MEDLINE]
Free PMC Article

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