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Utilisation de la métabolomique pour l'étude de l'encéphalopathie hépatique et développement de nouvelles approches pour l'acquisition de données par spectrométrie de masse

Pierre Barbier Saint Hilaire 1
1 LEMM - Laboratoire d'Etude du Métabolisme des Médicaments
SPI - Service de Pharmacologie et Immunoanalyse : DRF/JOLIOT
Abstract : Untargeted metabolomics aims at studying the whole metabolite content of biological media. This allows to assess phenotypic changes in these samples. In the frame of this work, a cohort of patients suffering from hepatic encephalopathy (HE) was studied using metabolomics, in association with lipidomics and glycomics. HE is a disease still poorly understood, but with high medical and social impact. This work, performed on cerebrospinal fluid and blood samples, demonstrates that HE is associated to an alteration of energy metabolism. Then, considering the limitations of metabolomics raised in our first study, we aim at developing new analytical chemistry methods for metabolomics. We demonstrate that the use of new instrument such as Orbitrap Fusion, which can reach very high resolution, gives acces to isotopic fine structure of metabolites, thus facilitating their identification. Furthermore, the study of ion fragmentation from MS² spectra enabled to better understand the involved mechanisms and should help for interpreting MS² spectra obtained from unknown metabolites. Finally, we showed that improvements achieved with the Orbitrap Fusion instrument in terms of data acquisition speed enables the implementation of new acquisition modes based on multi events MS and MS² acquisition, such as data dependent or data idependant acquisitions. All these improvements in the field of metabolomics should rapidly be applicable to medical cohort analyses.
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Pierre Barbier Saint Hilaire. Utilisation de la métabolomique pour l'étude de l'encéphalopathie hépatique et développement de nouvelles approches pour l'acquisition de données par spectrométrie de masse. Chimie analytique. Université Paris-Saclay, 2019. Français. ⟨NNT : 2019SACLS193⟩. ⟨tel-02435982⟩

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