Journal Article

Metabolomics analysis of human acute graft- versus-host disease reveals changes in host and microbiota-derived metabolites

Michonneau, David, DGOS. Alexion Pharmaceutical company (APALEX). Institut National du Cancer (project number INCa 2014-1-PL BIO-07-IP-1). Institut National du Cancer (INCa) and the Agence Nationale de la Recherche (ANR) under the auspices of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC), Socie, Gérard, Curis, Emmanuel, Robin, Marie, Ramamoorthy, Sivapriya, Dubouchet, Laetitia, Metabolon Inc, ANR-13-PRTS-0002,BioGvHD,Biomarqueurs de la maladie du greffon contre l'hôte et de la tolérance immunitaire chez l'homme, Peffault de Latour, Régis, Ingram, Brian, Chevret, Sylvie, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Latis, Eleonora, Immunorégulation - Immunoregulation ; Institut Pasteur [Paris] (IP), Service d'hématologie greffe [Saint-Louis] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe H

2019

Overview

Despite improvement in clinical management, allogeneic hematopoietic stem cell trans-plantation (HSCT) is still hampered by high morbidity and mortality rates, mainly due to graft versus host disease (GvHD). Recently, it has been demonstrated that the allogeneic immune response might be influenced by external factors such as tissues microenvironment or host microbiota. Here we used high throughput metabolomics to analyze two cohorts of geno-typically HLA-identical related recipient and donor pairs. Metabolomic profiles markedly differ between recipients and donors. At the onset of acute GvHD, in addition to host-derived metabolites, we identify significant variation in microbiota-derived metabolites, especially in aryl hydrocarbon receptor (AhR) ligands, bile acids and plasmalogens. Altogether, our findings support that the allogeneic immune response during acute GvHD might be influenced by bile acids and by the decreased production of AhR ligands by microbiota that could limit indoleamine 2,3-dioxygenase induction and influence allogeneic T cell reactivity.

• Publisher: Nature Publishing Group,CCSD,Nature Publishing Group UK,Nature Portfolio
• Subject: 631/250/1854 / 631/45/320 / 692/308/575 / 82/58 / Acute Disease / Adult / Aged / Bile Acids and Salts / Bile Acids and Salts - analysis / Bile Acids and Salts - immunology / Bile Acids and Salts - metabolism / Case-Control Studies / Cohort Studies / Female / Gastrointestinal Microbiome / Gastrointestinal Microbiome - physiology / Graft vs Host Disease / Graft vs Host Disease - blood / Graft vs Host Disease - etiology / Graft vs Host Disease - metabolism / Graft-versus-host reaction / Hematopoietic Stem Cell Transplantation / Hematopoietic Stem Cell Transplantation - adverse effects / Hematopoietic Stem Cell Transplantation - methods / Hematopoietic stem cells / Humanities and Social Sciences / Humans / Immune response / Immunology / Life Sciences / Ligands / Living Donors / Male / Metabolites / Metabolome / Metabolome - immunology / Metabolomics / Metabolomics - methods / Microbiota / Middle Aged / multidisciplinary / Plasmalogens / Plasmalogens - analysis / Plasmalogens - immunology / Plasmalogens - metabolism / Receptors, Aryl Hydrocarbon / Receptors, Aryl Hydrocarbon - immunology / Receptors, Aryl Hydrocarbon - metabolism / Science / Science (multidisciplinary) / Siblings / Stem cell transplantation / Stem cells / T-Lymphocytes / T-Lymphocytes - immunology / Transplantation / Transplantation, Homologous / Transplantation, Homologous - adverse effects / Transplantation, Homologous - methods / Transplants & implants / Tryptophan / Tryptophan - immunology / Tryptophan - metabolism / Young Adult
• ISBN: 0005027609000