Allogeneic hematopoietic cell transplantation, the microbiome, and graft-versus-host disease

Abstract

Many patients with hematological malignancies, such as acute myeloid leukemia, receive an allogeneic hematopoietic cell transplantation (HCT) to cure their underlying condition. Allogeneic HCT recipients are exposed to various elements during the pre-, peri- and post-transplant period that can disrupt intestinal microbiota, including chemo- and radiotherapy, antibiotics, and dietary changes. The dysbiotic post-HCT microbiome is characterized by low fecal microbial diversity, loss of anaerobic commensals, and intestinal domination, particularly by Enterococcus species, and is associated with poor transplant outcomes. Graft-versus-host disease (GvHD) is a frequent complication of allogeneic HCT caused by immunologic disparity between donor and host cells and results in tissue damage and inflammation. Microbiota injury is particularly pronounced in allogeneic HCT recipients who go on to develop GvHD. At present, manipulation of the microbiome for example, via dietary interventions, antibiotic stewardship, prebiotics, probiotics, or fecal microbiota transplantation, is widely being explored to prevent or treat gastrointestinal GvHD. This review discusses current insights into the role of the microbiome in GvHD pathogenesis and summarizes interventions to prevent and treat microbiota injury.

Determining the Optimal Use of Antibiotics in Hematopoietic Stem Cell Transplant Recipients

“…Furthermore, subgroup analyses found an association between lower intestinal diversity and higher risks of transplantation-related death and death attributable to GVHD . While the observational nature of the study by Peled et al introduces risk of biases—patients who were more severely ill may have had more cancer therapy, more health care, and more antibiotic exposure and thus were at higher risk of worse outcome, including mortality after allo-HCT—these findings were consistent with prior studies and the current understanding of the pathogenesis of microbiome injury …”

“…5 While the observational nature of the study by Peled et al 5 introduces risk of biases-patients who were more severely ill may have had more cancer therapy, more health care, and more antibiotic exposure and thus were at higher risk of worse outcome, including mortality after allo-HCT-these findings were consistent with prior studies and the current understanding of the pathogenesis of microbiome injury. 6,7 The results from the study by Rashidi et al 1 improve our understanding of the deleterious association of gut microbiota disruption with the development of aGVHD and contribute to risk vs benefit assessments in antibiotic prescribing. These findings 1 pave the way for designing and evaluating future antimicrobial stewardship interventions aimed at tailoring antibiotic regimens to minimize potential harms and maximize likelihood of benefits in patients undergoing allo-HCT.…”

Ecological insights into hematopoiesis regulation: unraveling the influence of gut microbiota

“…While statistical differences were not observed in this clinical trial, it still acknowledges the positive value of FMT in the context of HSCT. 118 , 119 Van den Brink’s lab explored the value of the intestinal microbiota in recipient hematopoietic system reconstruction after bone marrow transplantation. They found that in mice lacking intestinal microbiota, there is impaired hematopoietic system reconstruction after bone marrow transplantation.…”

Gut microbiome homeostasis and the future of probiotics in cancer immunotherapy

“…Future research should include mechanistic and interventional studies to explore the microbiome’s role in lymphoma responses and improve treatment outcomes ( 57 ). The success of fecal microbiota transplantation in other contexts provides evidence that the microbiome can be targeted for therapeutic intervention ( 69 ), Davar et al. ( 23 ).…”

“…Microbe-free formulations of probiotics may also be used. Immunotherapy can be combined with prebiotics, probiotics, postbiotics, and symbiotics in upcoming immune-oncology trials ( 69 ). The completed clinical trials testing the effect of probiotics on cancer immunotherapy is listed in Table 1 .…”