The Role of Intestinal Microbiota in Graft versus Host Disease

Graft versus host disease (GVHD) remains a major life threatening complication and one of the primary barriers to successful allogeneic hematopoietic stem cell transplantation, limiting its application in nonmalignant conditions. Immunosuppression is used for prevention and treatment of GVHD, dampening the graft versus leukemia effect. Intestinal bacteria play a major role in inflammation and augmenting the GVHD cytokine response. Early studies in murine models showed that manipulating the presence of intestinal flora or counteracting its byproducts could limit GVHD. Thus multiple clinical trials targeting gut decontamination were conducted, with the aims of modulating inflammation and protecting against GVHD, with mixed results. More recent work has improved our understanding of the role of intestinal microbiota in the maintenance of innate immunity, mucosal integrity and limiting inflammation. This review offers a summary of this data, with a discussion of potential therapeutic interventions manipulating the intestinal microbiota.