Obesity induces gut microbiota alterations and augments acute graft-versus-host disease after allogeneic stem cell transplantation
Lam T. Khuat, Catherine T. Le, Chien-Chun Steven Pai, Robin Shields‐Cutler, Shernan G. Holtan, Armin Rashidi, Sarah L. Parker, Dan Knights, Jesus I. Luna, Cordelia Dunai, Ziming Wang, Ian R. Sturgill, Kevin Stoffel, Alexander A. Merleev, Shyam K. More, Emanual Maverakis, Helen E. Raybould, Mingyi Chen, Robert J. Canter, Arta M. Monjazeb, Maneesh Dave, James L.M. Ferrara, John E. Levine, Dan L. Longo, Mehrdad Abedi, Bruce R. Blazar, William J. Murphy
Abstract
T cells and occurred even with a minor MHC mismatch between donor and recipient animals. Retrospective analysis of clinical cohorts receiving allo-HSCT transplants from unrelated donors revealed that recipients with a high body mass index (BMI, >30) had reduced survival and higher serum ST2 concentrations compared with nonobese transplant recipients. Assessment of both DIO mice and allo-HSCT recipients with a high BMI revealed reduced gut microbiota diversity and decreased Clostridiaceae abundance. Prophylactic antibiotic treatment protected DIO mouse recipients from endotoxin translocation across the gut and increased inflammatory cytokine production, as well as gut pathology and mortality, but did not protect against later development of chronic skin GVHD. These results suggest that obesity-induced alterations of the gut microbiota may affect GVHD after allo-HSCT in DIO mice, which could be ameliorated by prophylactic antibiotic treatment.