Faculty, Staff and Student Publications
Publication Date
2-14-2023
Journal
Immunity
Abstract
The severity of T cell-mediated gastrointestinal (GI) diseases such as graft-versus-host disease (GVHD) and inflammatory bowel diseases correlates with a decrease in the diversity of the host gut microbiome composition characterized by loss of obligate anaerobic commensals. The mechanisms underpinning these changes in the microbial structure remain unknown. Here, we show in multiple specific pathogen-free (SPF), gnotobiotic, and germ-free murine models of GI GVHD that the initiation of the intestinal damage by the pathogenic T cells altered ambient oxygen levels in the GI tract and caused dysbiosis. The change in oxygen levels contributed to the severity of intestinal pathology in a host intestinal HIF-1α- and a microbiome-dependent manner. Regulation of intestinal ambient oxygen levels with oral iron chelation mitigated dysbiosis and reduced the severity of the GI GVHD. Thus, targeting ambient intestinal oxygen levels may represent a novel, non-immunosuppressive strategy to mitigate T cell-driven intestinal diseases.
Keywords
Animals, Mice, Dysbiosis, Hematopoietic Stem Cell Transplantation, Intestines, Graft vs Host Disease, Gastrointestinal Diseases
DOI
10.1016/j.immuni.2023.01.007
PMID
36736321
PMCID
PMC11098523
PubMedCentral® Posted Date
May 2024
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Included in
Bioinformatics Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Medical Immunology Commons, Oncology Commons
Comments
Supplementary Materials
PMID: 36736321