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.
Highlights
Dramatic microbiota changes and loss of commensal anaerobic bacteria are associated with adverse outcomes in hematopoietic cell transplantation (HCT) recipients
Microbiome studies using fecal samples collected from allogeneic HCT patients have previously revealed that patients experience a severe reduction in the relative abundance of commensal bacteria over the course of treatment
Our cohort consisted of 18 patients who underwent auto- or allo-HCT at Memorial Sloan Kettering Cancer Center (MSKCC) between July 2015 and January 2016
Summary
Dramatic microbiota changes and loss of commensal anaerobic bacteria are associated with adverse outcomes in hematopoietic cell transplantation (HCT) recipients. Microbiome studies using fecal samples collected from allogeneic HCT (allo-HCT) patients have previously revealed that patients experience a severe reduction in the relative abundance of commensal bacteria over the course of treatment This loss can result in blooms of potentially pathogenic microbial species [3], leading to downstream complications such as infections and graft-versus-host disease (GVHD) [4,5,6]. Obligate anaerobic bacteria collected either approximately once per week or at a limited number of time points [3,4,5, 9, 10] Though these studies helped to form the foundation of our current understanding of microbiota disruption during allo-HCT, we posit that a more frequent stool sample collection scheme, combined with dynamic modeling, would be beneficial for providing a higher-resolution view of changes in microbiota composition over time and discerning individual antibiotic effects. Our results reveal how important commensal anaerobic microbial species are lost during HCT
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