Pre- and post-serial metagenomic analysis of gut microbiota as a prognostic factor in patients undergoing haematopoietic stem cell transplantation

Br J Haematol. 2020 Feb;188(3):438-449. doi: 10.1111/bjh.16205. Epub 2019 Sep 30.

Abstract

The human gut harbours diverse microorganisms, and gut dysbiosis has recently attracted attention because of its possible involvement in various diseases. In particular, the lack of diversity in the gut microbiota has been associated with complications of haematopoietic stem cell transplantation (HSCT), such as infections, acute graft-versus-host disease and relapse of primary disease, which lead to a poor prognosis. However, few studies have serially examined the composition of the intestinal microbiota after HSCT. In this study, we demonstrated, using next-generation sequencing of the bacterial 16S ribosomal RNA gene, combined with uniFrac distance analysis, that the intestinal microbiota of patients undergoing allogeneic HSCT substantially differed from that of healthy controls and recipients of autologous transplants. Faecal samples were obtained daily throughout the clinical course, before and after transplantation. Notably, the proportions of Bifidobacterium and genera categorized as butyrate-producing bacteria were significantly lower in patients with allogeneic HSCT than in healthy controls. Furthermore, among allogeneic transplant recipients, a subgroup with a preserved microbiota composition showed a benign course, whereas patients with a skewed microbiota showed a high frequency of complications and mortality after transplantation. Thus, we conclude that the stability of intestinal microbiota is critically involved in outcomes of HSCT.

Keywords: beta-diversity; gut microbiota; next-generation sequencing; stem cell transplantation; uniFrac analysis.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Allografts
  • Autografts
  • Bacterial Typing Techniques
  • Bifidobacterium / isolation & purification
  • Case-Control Studies
  • DNA, Bacterial / genetics
  • Dysbiosis / complications
  • Dysbiosis / microbiology
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Intestines / microbiology
  • Male
  • Metagenomics / methods
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • RNA, Ribosomal, 16S / genetics
  • Survival Analysis
  • Transplantation Conditioning / methods

Substances

  • DNA, Bacterial
  • RNA, Ribosomal, 16S