Obesity induces gut microbiota alterations and augments acute graft-versus-host disease after allogeneic stem cell transplantation

Lam T. Khuat(University of California, Davis), Catherine T. Le(University of California, Davis), Chien-Chun Steven Pai(University of California, Davis), Robin Shields‐Cutler(Macalester College), Shernan G. Holtan(University of Minnesota), Armin Rashidi(University of Minnesota), Sarah L. Parker(University of Minnesota), Dan Knights(Biotechnology Institute), Jesus I. Luna(University of California, Davis), Cordelia Dunai(University of California, Davis), Ziming Wang(University of California, Davis), Ian R. Sturgill(University of California, Davis), Kevin Stoffel(University of California, Davis), Alexander A. Merleev(University of California, Davis), Shyam K. More(University of California, Davis), Emanual Maverakis(University of California, Davis), Helen E. Raybould(University of California, Davis), Mingyi Chen(Southwestern Medical Center), Robert J. Canter(University of California, Davis), Arta M. Monjazeb(University of California, Davis), Maneesh Dave(University of California, Davis), James L.M. Ferrara(Icahn School of Medicine at Mount Sinai), John E. Levine(Icahn School of Medicine at Mount Sinai), Dan L. Longo(Harvard University), Mehrdad Abedi(University of California, Davis), Bruce R. Blazar(University of Minnesota Medical Center), William J. Murphy(University of California, Davis)
Science Translational Medicine
November 25, 2020
10.1126/scitranslmed.aay7713
Cited by 50Open Access
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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.

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