Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation

Keisuke Seike, Anders Kiledal, Hideaki Fujiwara, Israel Henig, Marina Burgos da Silva, Marcel R.M. van den Brink, Robert Hein, Matthew Hoostal, Chen Liu, Katherine Oravecz-Wilson, Emma Lauder, Lu Li, Yaping Sun, Thomas M. Schmidt, Yatrik M. Shah, Robert R. Jenq, Gregory Dick, Pavan Reddy

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)353-368.e6
JournalImmunity
Volume56
Issue number2
DOIs
StatePublished - Feb 14 2023

Keywords

  • T cell-mediated gastrointestinal (GI) diseases
  • allogeneic
  • germ-free
  • graft-versus-host host disease
  • hypoxia
  • iron chelation
  • microbiome
  • oxygen
  • tissue tolerance
  • transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

MD Anderson CCSG core facilities

  • Research Animal Support Facility

Fingerprint

Dive into the research topics of 'Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation'. Together they form a unique fingerprint.

Cite this