Recent findings published in Immunity have found that changes in gastrointestinal (GI) oxygen levels, mediated by graft-versus-host disease (GVHD), lead to reduced host gut microbiome composition and activity (a process known as dysbiosis). These changes in oxygen levels contribute to the severity of observed GI pathology in a host intestinal HIF-1α- and a microbiome-dependent manner. Modulating oxygen levels to prevent serious GI tract damage may lead to novel therapeutics for GVHD symptoms.

GVHD is a serious and common complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) that can cause inflammation of the gut lining. This can lead to serious symptoms such as diarrhea, abdominal pain, vomiting, and nausea. Recent research suggests that the gut microbiome could be a major factor in the development of GVHD. Studies have shown that individuals with GVHD tend to have a different composition of bacteria in their gut compared to individuals without GVHD. Furthermore, there is evidence that manipulating the composition of the gut microbiome can reduce the severity of GVHD symptoms. In this study, the authors sought to determine if dysbiosis is caused by or is a consequence of severe GVHD, what causes dysbiosis, and if dysbiosis can influence GVHD severity.

The authors found that the initiation of intestinal damage caused by the pathogenic T cells altered the ambient oxygen levels in the GI tract, leading to dysbiosis and contributing to the severity of the pathology. Interestingly, dysbiosis prior to HSCT did not impact the severity of GVHD, but post-HCT dysbiosis was found to be a consequence of the changes in intestinal luminal oxygen level from tissue injury caused by GVHD. Further, using a mouse model, they demonstrated that regulating oxygen levels with oral iron chelation mitigated dysbiosis and reduced the severity of GI GVHD. These findings suggest that targeting ambient intestinal oxygen levels may be a novel, non-immunosuppressive strategy to mitigate T cell-driven intestinal diseases.

Reference:

Seike K, Kiledal A, Fujiwara H, et al. Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation. Immunity. 2023;56(2):353-368.e6. doi:10.1016/j.immuni.2023.01.007

Tags: AlloHCT, GVHD, Allogeneic, Graft function, grafts, graft, Allo HCT, graft-versus-host disease, graft-vs-host disease, allogeneic stem cell transplantation, T cells, T cell, graft-versus-host