Metabolic Potential of the Gut Microbiome Is Significantly Impacted by Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation Recipients

Mette Jørgensen*, Jens C Nørgaard, Emma E Ilett, Ramtin Z Marandi, Marc Noguera-Julian, Roger Paredes, Daniel D Murray, Jens Lundgren, Cameron Ross MacPherson, Henrik Sengeløv*

*Corresponding author for this work

Abstract

Allogeneic hematopoietic stem cell transplantation (aHSCT) is a putative curative treatment for malignant hematologic disorders. During transplantation, the immune system is suppressed/eradicated through a conditioning regimen (non-myeloablative or myeloablative) and replaced with a donor immune system. In our previous study, we showed changes in gut taxonomic profiles and a decrease in bacterial diversity post-transplant. In this study, we expand the cohort with 114 patients and focus on the impact of the conditioning regimens on taxonomic features and the metabolic functions of the gut bacteria. This is, to our knowledge, the first study to examine the metabolic potential of the gut microbiome in this patient group. Adult aHSCT recipients with shotgun sequenced stool samples collected day -30 to +28 relative to aHSCT were included. One sample was selected per patient per period: pre-aHSCT (day -30-0) and post-aHSCT (day 1-28). In total, 254 patients and 365 samples were included. Species richness, alpha diversity, gene richness and metabolic richness were all lower post-aHSCT than pre-aHSCT and the decline was more pronounced for the myeloablative group. The myeloablative group showed a decline in 36 genera and an increase in 15 genera. For the non-myeloablative group, 30 genera decreased and 16 increased with lower fold changes than observed in the myeloablative group. For the myeloablative group, 32 bacterial metabolic functions decreased, and one function increased. For the non-myeloablative group, three functions decreased, and two functions increased. Hence, the changes in taxonomy post-aHSCT caused a profound decline in bacterial metabolic functions especially in the myeloablative group, thus providing new evidence for associations of myeloablative conditioning and gut dysbiosis from a functional perspective.

Original languageEnglish
Article number11115
JournalInternational Journal of Molecular Sciences
Volume23
Issue number19
ISSN1661-6596
DOIs
Publication statusPublished - 21 Sept 2022

Keywords

  • Adult
  • Gastrointestinal Microbiome
  • Hematologic Neoplasms/therapy
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immune System/pathology
  • Transplantation Conditioning

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