The Microbiome, Inflammation, and GVHD Axis: The Balance Between the “Gut” and the Bad

Hematopoietic stem cell transplantation is one of the most intricate immune therapies used for patients with hematological diseases or immune disorders. In addition to the inherent immunosuppression from their primary condition, many of these patients usually receive cytotoxic chemotherapy, radiation therapy, broad-spectrum antibiotics, or experience extended nutritional perturbations. These factors collectively lead to inflammation and the disruption of gut microbiota. Additionally, about 40–60% of patients undergoing fully HLA-matched allogeneic transplantation are expected to develop acute graft-versus-host disease (aGVHD), even with prophylactic measures such as calcineurin inhibitors, methotrexate/mycophenolate, or post-transplant cyclophosphamide treatment. Recent research has elucidated the complex interplay between immune effectors in the gastrointestinal tract and microbial populations within a proinflammatory peri-transplant environment, revealing its significant effect on survival and post-transplant complications such as aGVHD. This review will explore the relationship between dysbiosis during allogeneic transplantation and mechanisms that can help clarify the link between gut microbiota and the risk of GVHD, along with emerging therapeutic strategies aimed at addressing dysbiosis during hematopoietic stem cell transplantation.