TY - JOUR
T1 - The Microbiome and Its Impact on Allogeneic Hematopoietic Cell Transplantation
AU - Malard, Florent
AU - Jenq, Robert R.
N1 - Publisher Copyright:
© Wolters Kluwer Health, Inc.
PY - 2023/3/1
Y1 - 2023/3/1
N2 - Allogeneic hematopoietic cell transplantation (alloHCT) is a standard curative therapy for a variety of benign and malignant hematological diseases. Previously, patients who underwent alloHCT were at high risk for complications with potentially life-threatening toxicities, including a variety of opportunistic infections as well as acute and chronic manifestations of graft-versus-host disease (GVHD), where the transplanted immune system can produce inflammatory damage to the patient. With recent advances, including newer conditioning regimens, advances in viral and fungal infection prophylaxis, and novel GVHD prophylactic and treatment strategies, improvements in clinical outcomes have steadily improved. One modality with great potential that has yet to be fully realized is targeting the microbiome to further improve clinical outcomes. In recent years, the intestinal microbiota, which includes bacteria, fungi, viruses, and other microbes that reside within the intestinal tract, has become established as a potent modulator of alloHCT outcomes. The composition of intestinal bacteria, in particular, has been found in large multicenter prospective studies to be strongly associated with GVHD, treatment-related mortality, and overall survival. Murine studies have demonstrated a causal relationship between intestinal microbiota injury and aggravated GVHD, and more recently, clinical interventional studies of repleting the intestinal microbiota with fecal microbiota transplantation have emerged as effective therapies for GVHD. How the composition of the intestinal bacterial microbiota, which is often highly variable in alloHCT patients, can modulate GVHD and other outcomes is not fully understood. Recent studies, however, have begun to make substantial headway, including identifying particular bacterial subsets and/or bacterial-derived metabolites that can mediate harm or benefit. Here, the authors review recent studies that have improved our mechanistic understanding of the relationship between the microbiota and alloHCT outcomes, as well as studies that are beginning to establish strategies to modulate the microbiota with the hope of optimizing clinical outcomes.
AB - Allogeneic hematopoietic cell transplantation (alloHCT) is a standard curative therapy for a variety of benign and malignant hematological diseases. Previously, patients who underwent alloHCT were at high risk for complications with potentially life-threatening toxicities, including a variety of opportunistic infections as well as acute and chronic manifestations of graft-versus-host disease (GVHD), where the transplanted immune system can produce inflammatory damage to the patient. With recent advances, including newer conditioning regimens, advances in viral and fungal infection prophylaxis, and novel GVHD prophylactic and treatment strategies, improvements in clinical outcomes have steadily improved. One modality with great potential that has yet to be fully realized is targeting the microbiome to further improve clinical outcomes. In recent years, the intestinal microbiota, which includes bacteria, fungi, viruses, and other microbes that reside within the intestinal tract, has become established as a potent modulator of alloHCT outcomes. The composition of intestinal bacteria, in particular, has been found in large multicenter prospective studies to be strongly associated with GVHD, treatment-related mortality, and overall survival. Murine studies have demonstrated a causal relationship between intestinal microbiota injury and aggravated GVHD, and more recently, clinical interventional studies of repleting the intestinal microbiota with fecal microbiota transplantation have emerged as effective therapies for GVHD. How the composition of the intestinal bacterial microbiota, which is often highly variable in alloHCT patients, can modulate GVHD and other outcomes is not fully understood. Recent studies, however, have begun to make substantial headway, including identifying particular bacterial subsets and/or bacterial-derived metabolites that can mediate harm or benefit. Here, the authors review recent studies that have improved our mechanistic understanding of the relationship between the microbiota and alloHCT outcomes, as well as studies that are beginning to establish strategies to modulate the microbiota with the hope of optimizing clinical outcomes.
KW - Allogeneic
KW - graft-versus-host disease
KW - hematopoietic cell transplantation
KW - microbiome
KW - microbiota
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U2 - 10.1097/PPO.0000000000000645
DO - 10.1097/PPO.0000000000000645
M3 - Review article
C2 - 36957977
AN - SCOPUS:85150930335
SN - 1528-9117
VL - 29
SP - 75
EP - 83
JO - Cancer Journal (United States)
JF - Cancer Journal (United States)
IS - 2
ER -