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...
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MDPI AG
2022-09-01
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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> |
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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 |
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