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

David Michonneau (1, 2) , Eleonora Latis (3) , Emmanuel Curis (4, 5) , Laetitia Dubouchet (2) , Sivapriya Ramamoorthy (6) , Brian Ingram (6) , Régis Peffault de Latour (1, 2) , Marie Robin (1) , Flore Sicre de Fontbrune (1) , Sylvie Chevret (7, 4) , Lars Rogge (3) , Gérard Socie (1, 2)

1 Service d'hématologie greffe [Saint-Louis]
2 HIPI (UMR_S_976 / U976) - Immunologie humaine, physiopathologie & immunothérapie
3 Immunorégulation - Immunoregulation
4 Service de biostatistiques et information médicale [Saint-Louis]
5 BioSTM - EA 7537 - Biostatistique, traitement et modélisation des données biologiques
6 Metabolon INC
7 CRESS (U1153 / UMR_A_1125 / UMR_S_1153) - Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité

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.

Keywords: Translational Research; Metabolomics; Transplant Immunology

Domains: Life Sciences [q-bio]; Immunology

David Michonneau, Eleonora Latis, Emmanuel Curis, Laetitia Dubouchet, Sivapriya Ramamoorthy, et al.. Metabolomics analysis of human acute graft- versus-host disease reveals changes in host and microbiota-derived metabolites. Nature Communications, 2019, 10 (1), pp.5695. ⟨10.1038/s41467-019-13498-3⟩. ⟨pasteur-02626069⟩