Antibiotic-induced shifts in fecal microbiota density and composition during hematopoietic stem cell transplantation

Abstract

Background 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. Methods We collected 272 longitudinal stool samples (with mostly daily frequency) from 18 patients undergoing HCT and determined their composition by multi-parallel 16S rRNA gene sequencing, as well as density of bacteria in stool by qPCR. We calculated microbiota volatility to quantify rapid shifts and developed a new dynamic systems inference method to assess the specific impact of antibiotics. Results 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. Conclusions 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.