期刊
INFECTION AND IMMUNITY
卷 87, 期 9, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.00206-19
关键词
antibiotics; commensal anaerobes; hematopoietic cell transplantation; microbiome; systems biology
资金
- Seres Therapeutics
- Jazz Pharmaceuticals
- Therakos
- Merck Co., Inc.
- DKMS Medical Council
- Juno Therapeutics
- National Institutes of Health [U01Al124275-03, R01-CA228358, P30 CA008748]
- MSK Cancer Center Support Grant/Core Grant [4 of P01-CA023766]
- Parker Institute for Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center
- Sawiris Foundation
- Society of Memorial Sloan Kettering Cancer Center
- MSKCC Cancer Systems Immunology Pilot Grant
- Empire Clinical Research Investigator Program
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.
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