Circulating microbial cell-free DNA is increased during neutropenia following hematopoietic stem cell transplantation.

Abstract

We used a next-generation sequencing platform to characterize microbial cell-free DNA (mcfDNA) in plasma samples from patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT). In this observational study, we sought to characterize plasma mcfDNA in order to understand its potential association with the immunologic complications of transplantation. We compared serially-collected patient samples with plasma collected from healthy control subjects. We observed changes in total mcfDNA burden in plasma after transplantation, which was most striking during the early post-transplant neutropenic phase. This elevation could be attributed to a number of specific bacterial taxa, including Veillonella, Bacteroides and Prevotella (genus level). For an additional cohort of patients, we compared mcfDNA from plasma with 16S-rRNA sequencing data from stool samples collected at matched time points. In a number of patients, we confirmed that mcfDNA derived from specific microbial taxa (e.g. Enterococcus) could also be observed in the matched stool sample. Quantification of mcfDNA may generate novel insights into mechanisms by which the intestinal microbiome influences systemic cell populations and thus has been associated with outcomes for cancer patients.