Abstract

BackgroundBacteremia, or bloodstream infection (BSI), is a leading cause of death among patients with certain types of cancer. A previous study reported that intestinal domination, defined as occupation of at least 30 % of the microbiota by a single bacterial taxon, is associated with BSI in patients undergoing allo-HSCT. However, the impact of the intestinal microbiome before treatment initiation on the risk of subsequent BSI remains unclear. Our objective was to characterize the fecal microbiome collected before treatment to identify microbes that predict the risk of BSI.MethodsWe sampled 28 patients with non-Hodgkin lymphoma undergoing allogeneic hematopoietic stem cell transplantation (HSCT) prior to administration of chemotherapy and characterized 16S ribosomal RNA genes using high-throughput DNA sequencing. We quantified bacterial taxa and used techniques from machine learning to identify microbial biomarkers that predicted subsequent BSI.ResultsWe found that patients who developed subsequent BSI exhibited decreased overall diversity and decreased abundance of taxa including Barnesiellaceae, Coriobacteriaceae, Faecalibacterium, Christensenella, Dehalobacterium, Desulfovibrio, and Sutterella. Using machine-learning methods, we developed a BSI risk index capable of predicting BSI incidence with a sensitivity of 90 % at a specificity of 90 % based only on the pretreatment fecal microbiome.ConclusionsThese results suggest that the gut microbiota can identify high-risk patients before HSCT and that manipulation of the gut microbiota for prevention of BSI in high-risk patients may be a useful direction for future research. This approach may inspire the development of similar microbiome-based diagnostic and prognostic models in other diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0301-4) contains supplementary material, which is available to authorized users.

Highlights

  • Bacteremia, or bloodstream infection (BSI), is a leading cause of death among patients with certain types of cancer

  • A frequent side effect of myeloablative doses of chemotherapy used during the Hematopoietic stem cell transplantation (HSCT) procedure is gastro-intestinal (GI) mucositis [2]

  • While the model of pathobiology of mucositis reported above is silent on the role of the intestinal microbiome, Van Vliet et al proposed a potential role for the intestinal microbiome in BSI [9]

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Summary

Introduction

Bacteremia, or bloodstream infection (BSI), is a leading cause of death among patients with certain types of cancer. The impact of the intestinal microbiome before treatment initiation on the risk of subsequent BSI remains unclear. A recent model, introduced by Sonis, described a process for bacterial infection due to GI mucositis [3]. It includes an ulcerative phase with increased permeability. BSI is frequent during the early transplant period due to the intensive chemotherapy regimen administered prior to HSCT [8], but there is currently no way to predict or prevent it. A previous study reported that intestinal domination, defined as occupation of at least 30 % of the microbiota by a single bacterial taxon, is associated with BSI in patients undergoing allo-HSCT [10]

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