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


Journal

Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086

Informations de publication

Date de publication:
25 11 2020
Historique:
received: 17 07 2019
revised: 22 01 2020
accepted: 02 06 2020
entrez: 26 11 2020
pubmed: 27 11 2020
medline: 24 6 2021
Statut: ppublish

Résumé

The efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by acute and chronic graft-versus-host disease (GVHD). The impact of obesity on allo-HSCT outcomes is poorly understood. Here, we report that obesity had a negative and selective impact on acute gut GVHD after allo-HSCT in mice with diet-induced obesity (DIO). These animals exhibited increased gut permeability, endotoxin translocation across the gut, and radiation-induced gastrointestinal damage after allo-HSCT. After allo-HSCT, both male and female DIO mouse recipients showed increased proinflammatory cytokine production and expression of the GVHD marker ST2 (IL-33R) and MHC class II molecules; they also exhibited decreased survival associated with acute severe gut GVHD. This rapid-onset, obesity-associated gut GVHD depended on donor CD4

Identifiants

pubmed: 33239390
pii: 12/571/eaay7713
doi: 10.1126/scitranslmed.aay7713
pmc: PMC8525601
mid: NIHMS1742820
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NCI NIH HHS
ID : P30 CA093373
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK092993
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA065493
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL118979
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI034495
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL155114
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA214048
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL056067
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA039542
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK110421
Pays : United States

Informations de copyright

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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Auteurs

Lam T Khuat (LT)

Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Catherine T Le (CT)

Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Chien-Chun Steven Pai (CS)

Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Robin R Shields-Cutler (RR)

Department of Biology, Macalester College, Saint Paul, MN 55105, USA.

Shernan G Holtan (SG)

Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA.

Armin Rashidi (A)

Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA.

Sarah L Parker (SL)

Department of Internal Medicine, University of Minnesota, Minneapolis, MN 55455, USA.

Dan Knights (D)

Department of Computer Science and Engineering, Biotechnology Institute, University of Minnesota, Minneapolis, MN 55455, USA.

Jesus I Luna (JI)

Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Cordelia Dunai (C)

Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Ziming Wang (Z)

Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Ian R Sturgill (IR)

Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Kevin M Stoffel (KM)

Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Alexander A Merleev (AA)

Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Shyam K More (SK)

Division of Gastroenterology, Department of Internal Medicine, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Emanual Maverakis (E)

Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Helen E Raybould (HE)

Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.

Mingyi Chen (M)

Department of Pathology and Laboratory Medicine, UT Southwestern Medical Center, Dallas, TX 75390, USA.

Robert J Canter (RJ)

Division of Surgical Oncology, Department of Surgery, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Arta M Monjazeb (AM)

Department of Radiation Oncology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Maneesh Dave (M)

Division of Gastroenterology, Department of Internal Medicine, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

James L M Ferrara (JLM)

Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

John E Levine (JE)

Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Dan L Longo (DL)

Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

Mehrdad Abedi (M)

Department of Internal Medicine, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

Bruce R Blazar (BR)

Masonic Cancer Center and Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.

William J Murphy (WJ)

Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA. wmjmurphy@ucdavis.edu.
Department of Internal Medicine, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.

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