The Gut Microbiota and Immune System Relationship in Human Graft-versus-Host Disease

Abstract

Gut microbiota has gained increasing interest in the pathogenesis of immune-related diseases. In this context, graft-versus-host disease is a condition characterized by an immune response which frequently complicates and limits the outcomes of hematopoietic stem cell transplantations. Past studies, carried mostly in animals, already supported a relationship between gut microbiota and graft-versus-host disease. However, the possible mechanisms underlying this connection remain elusory. Moreover, strategies to prevent graft-versus-host disease are of great interest as well as the potential role of gut microbiota modulation. We reviewed the role of gut microbiota in the development of immune system and its involvement in the graft-versus-host disease, focusing on data available on humans.

Figure 1

The gut barrier and its alterations during the pathogenesis of GVHD. The healthy gut barrier is essential to maintain the immune homeostasis. Total body irradiation and/or chemotherapy, used as conditioning regimen, lead to gut barrier disruption, damaging the mucus layer and the epithelium. Thus, bacteria and bacterial products such as lipopolysaccharide translocate in the lamina propria where, together with endogenous danger molecules released from damaged epithelial cells, activate host and/or donor antigen-presenting cells (APCs) which prime alloreactive donor-derived T cells, triggering the damage to target organs. Modified from Heidegger.