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

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 sys...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/19/11115
_version_ 1797479215819390976
author 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
author_facet 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
author_sort Mette Jørgensen
collection DOAJ
description 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<b>.</b>
first_indexed 2024-03-09T21:42:35Z
format Article
id doaj.art-d52d39ab6a0543349336e38cc011ebe9
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-09T21:42:35Z
publishDate 2022-09-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-d52d39ab6a0543349336e38cc011ebe92023-11-23T20:27:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123191111510.3390/ijms231911115Metabolic Potential of the Gut Microbiome Is Significantly Impacted by Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation RecipientsMette Jørgensen0Jens C. Nørgaard1Emma E. Ilett2Ramtin Z. Marandi3Marc Noguera-Julian4Roger Paredes5Daniel D. Murray6Jens Lundgren7Cameron Ross MacPherson8Henrik Sengeløv9CHIP Centre of Excellence, Rigshospitalet, 2100 Copenhagen, DenmarkCHIP Centre of Excellence, Rigshospitalet, 2100 Copenhagen, DenmarkCHIP Centre of Excellence, Rigshospitalet, 2100 Copenhagen, DenmarkCHIP Centre of Excellence, Rigshospitalet, 2100 Copenhagen, DenmarkInstitut de Recerca de la SIDA–IrsiCaixa, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, SpainInstitut de Recerca de la SIDA–IrsiCaixa, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, SpainCHIP Centre of Excellence, Rigshospitalet, 2100 Copenhagen, DenmarkCHIP Centre of Excellence, Rigshospitalet, 2100 Copenhagen, DenmarkCHIP Centre of Excellence, Rigshospitalet, 2100 Copenhagen, DenmarkDepartment of Haematology, Rigshospitalet, 2100 Copenhagen, DenmarkAllogeneic 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<b>.</b>https://www.mdpi.com/1422-0067/23/19/11115allogeneic hematopoietic stem cell transplantation (aHSCT)conditioning regimenmetabolic potentialgut microbiomewhole genome sequencing
spellingShingle 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
Metabolic Potential of the Gut Microbiome Is Significantly Impacted by Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation Recipients
International Journal of Molecular Sciences
allogeneic hematopoietic stem cell transplantation (aHSCT)
conditioning regimen
metabolic potential
gut microbiome
whole genome sequencing
title Metabolic Potential of the Gut Microbiome Is Significantly Impacted by Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation Recipients
title_full Metabolic Potential of the Gut Microbiome Is Significantly Impacted by Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation Recipients
title_fullStr Metabolic Potential of the Gut Microbiome Is Significantly Impacted by Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation Recipients
title_full_unstemmed Metabolic Potential of the Gut Microbiome Is Significantly Impacted by Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation Recipients
title_short Metabolic Potential of the Gut Microbiome Is Significantly Impacted by Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation Recipients
title_sort metabolic potential of the gut microbiome is significantly impacted by conditioning regimen in allogeneic hematopoietic stem cell transplantation recipients
topic allogeneic hematopoietic stem cell transplantation (aHSCT)
conditioning regimen
metabolic potential
gut microbiome
whole genome sequencing
url https://www.mdpi.com/1422-0067/23/19/11115
work_keys_str_mv AT mettejørgensen metabolicpotentialofthegutmicrobiomeissignificantlyimpactedbyconditioningregimeninallogeneichematopoieticstemcelltransplantationrecipients
AT jenscnørgaard metabolicpotentialofthegutmicrobiomeissignificantlyimpactedbyconditioningregimeninallogeneichematopoieticstemcelltransplantationrecipients
AT emmaeilett metabolicpotentialofthegutmicrobiomeissignificantlyimpactedbyconditioningregimeninallogeneichematopoieticstemcelltransplantationrecipients
AT ramtinzmarandi metabolicpotentialofthegutmicrobiomeissignificantlyimpactedbyconditioningregimeninallogeneichematopoieticstemcelltransplantationrecipients
AT marcnoguerajulian metabolicpotentialofthegutmicrobiomeissignificantlyimpactedbyconditioningregimeninallogeneichematopoieticstemcelltransplantationrecipients
AT rogerparedes metabolicpotentialofthegutmicrobiomeissignificantlyimpactedbyconditioningregimeninallogeneichematopoieticstemcelltransplantationrecipients
AT danieldmurray metabolicpotentialofthegutmicrobiomeissignificantlyimpactedbyconditioningregimeninallogeneichematopoieticstemcelltransplantationrecipients
AT jenslundgren metabolicpotentialofthegutmicrobiomeissignificantlyimpactedbyconditioningregimeninallogeneichematopoieticstemcelltransplantationrecipients
AT cameronrossmacpherson metabolicpotentialofthegutmicrobiomeissignificantlyimpactedbyconditioningregimeninallogeneichematopoieticstemcelltransplantationrecipients
AT henriksengeløv metabolicpotentialofthegutmicrobiomeissignificantlyimpactedbyconditioningregimeninallogeneichematopoieticstemcelltransplantationrecipients