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

David Michonneau, Eleonora Latis, Emmanuel Curis, Laetitia Dubouchet, Sivapriya Ramamoorthy, Brian Ingram, Régis Peffault Latour, Marie Robin, Flore Sicre Fontbrune, Sylvie Chevret, Lars Rogge and Gérard Socié ()
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David Michonneau: Saint Louis Hospital
Eleonora Latis: Department of Immunology
Emmanuel Curis: Université de Paris, INSERM UMR-S1144
Laetitia Dubouchet: Université de Paris
Sivapriya Ramamoorthy: Metabolon, Inc.
Brian Ingram: Metabolon, Inc.
Régis Peffault Latour: Saint Louis Hospital
Marie Robin: Saint Louis Hospital
Flore Sicre Fontbrune: Saint Louis Hospital
Sylvie Chevret: Hôpital Saint-Louis
Lars Rogge: Department of Immunology
Gérard Socié: Saint Louis Hospital

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Despite improvement in clinical management, allogeneic hematopoietic stem cell transplantation (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 genotypically 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.

Date: 2019
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DOI: 10.1038/s41467-019-13498-3

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