Microbiome: An Emerging New Frontier in Graft-Versus-Host Disease

Hematopoietic cell transplantation is an intensive therapy used to treat high-risk hematological malignant disorders and other life-threatening hematological and genetic diseases. Graft-versus-host disease (GVHD) presents a barrier to its wider application. A conditioning regimen and medications given to patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) are capable of disturbing the homeostatic crosstalk between the microbiome and the host immune system and of leading to dysbiosis. Intestinal inflammation in the context of GVHD is associated with loss in microbial diversity that could serve as an independent predictor of mortality. Successful gastrointestinal decontamination using high doses of non-absorbable antibiotics likely affect allo-HCT outcomes leading to significantly less acute GVHD (aGVHD). Butyrate-producing Clostridia directly result in the increased presence of regulatory T cells in the gut, which are protective in GVHD development. Beyond the microbiome, Candida, a member of the mycobiome, colonization in the gut has been considered as a risk factor in pathophysiology of aGVHD and reduction in GVHD is observed with antifungal prophylaxis with fluconazole. Reduced number of goblet cells and Paneth cells have been shown to associate with GVHD and has a significant impact on the micro- and mycobiome density and their composition. Lower levels of 3-indoxyl sulfate at initial stages after allo-HCT are related with worse GVHD outcomes and increased mortality. Increased understanding of the vital role of the gut microbiome in GVHD can give directions to move the field towards the development of improved innovative approaches for preventing or treating GVHD following allo-HCT.