Metabolomics

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Metabolomics analysis of human acute graft-versus-host disease reveals changes in host and microbiota-derived metabolites (Cohort 1)


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 (UPLC-MS/MS) in two cohorts of genotypically HLA-identical related recipient and donor pairs. A first monocentric cohort from Saint Louis hospital (Paris, France) was used as an exploratory cohort (n=43) and a second multicentric national cohort from Cryostem biobank was used as a confimatory cohort (n=56).

Metabolomic profile markedly differed between recipients and donors. At the onset of acute GvHD, in addition to host-derived metabolites, we identified 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 (IDO) induction and influence allogeneic T-cell reactivity.


MTBLS204 contains study information relating to cohort 1.

MTBLS205 contains study information relating to cohort 2.

INSTRUMENT(S): Q Exactive

SUBMITTER: David Michonneau 

PROVIDER: MTBLS204 | MetaboLights | 2019-11-06

REPOSITORIES: MetaboLights

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

Michonneau David D   Latis Eleonora E   Curis Emmanuel E   Dubouchet Laetitia L   Ramamoorthy Sivapriya S   Ingram Brian B   de Latour Régis Peffault RP   Robin Marie M   de Fontbrune Flore Sicre FS   Chevret Sylvie S   Rogge Lars L   Socié Gérard G  

Nature communications 20191213 1


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  ...[more]

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