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.

KEYWORDS:

• Allogeneic HCT
• GvHD
• gut microbiome
• gut microbiota
• FMT
• mucosal immune system

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by an anonymous donation via the AMC Foundation (YFvL), an intramural grant from the Academic Medical Center (YFvL), a VIDI grant (NWO ZonMW #91715362) (MDH), and a LSBR Fellowship (1438F) (MDH; Landsteiner Foundation for Blood Transfusion Research.