Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-019-13498-3
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Funding
- Alexion Company
- Direction Generale de l'Offre de Soins (DGOS)
- Agence National de la Recherche (ANR) within a Projet de Recherche Translationnelle en Sante [ANR-PRTS 13002]
- Alexion Pharmaceutical company (APALEX)
- Institut National du Cancer [INCa 2014-1-PL BIO-07-IP-1]
- Institut National du Cancer (INCa)
- Agence Nationale de la Recherche (ANR)
- Societe Francophone de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC)
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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.
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