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.
Highlights
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)
In addition to the above described pathways, we identified a strong increase of multiple complex lipid products in patients with acute GvHD, such as medium- and long-chain fatty acid, polyunsaturated fatty acid (n3 and n6) and in primary and secondary bile acids (BAs) (Fig. 4b, c, Supplementary Fig. 3b, c, Supplementary Data 11 and 12)
GvHD is an immune reaction from donor immune cells targeting allogeneic antigens in recipients, whose pathophysiology is still only partially understood in humans
Summary
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). Allogeneic hematopoietic stem cell transplantation (HSCT) is a major treatment for hematologic malignancies and for inherited or acquired hematopoiesis disorders It is still hampered by high morbidity and mortality rates[1] mainly due to graft-versus-host disease (GvHD). At acute GVHD onset, significant variation of host- and microbiota-derived metabolites are identified, mainly affecting indole compounds of the tryptophan metabolism, a group of metabolites that acts as ligands for the aryl hydrocarbon receptor (AhR), together with bile acids (BAs) and plasmalogens. This suggests that dysbiosis, together with transplantation-related alteration of host metabolism, induce major change in circulating metabolites in recipients that might influence allogeneic immune cell reactivity
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