Untargeted Plasma Metabolomics Extends the Biomarker Profile of Mitochondrial Neurogastrointestinal Encephalomyopathy

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dc.contributor.authorBax, Bridget E.
dc.contributor.authorUcar, Sema Kalkan
dc.date.accessioned2026-09-26T19:10:26Z
dc.date.available2026-09-26T19:10:26Z
dc.date.issued2025
dc.departmentEge Üniversitesi
dc.description.abstractMitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by pathogenic mutations in the nuclear TYMP gene, which encodes the cytosolic enzyme thymidine phosphorylase. In addition to the systemic accumulation of thymidine and deoxyuridine, several case studies have reported abnormalities in a range of other metabolites in patients with MNGIE. Since metabolites are intermediates or end-products of numerous biochemical reactions, they serve as highly informative indicators of an organism's metabolic activity. This study aimed to perform an untargeted metabolomic profiling to determine whether individuals with MNGIE exhibit a distinct plasma metabolic signature compared to 15 age- and sex-matched healthy controls. Metabolites were profiled using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry (UHPLC-MS). A total of 160 metabolites were found to be significantly upregulated and 260 downregulated in patients with MNGIE. KEGG pathway enrichment analysis revealed disruptions in 20 metabolic pathways, with arachidonic acid metabolism and bile acid biosynthesis being the most significantly upregulated. Univariate receiver operating characteristic (ROC) curve analyses identified 23 individual metabolites with diagnostic potential, each showing an area under the curve (AUC) >= 0.80. We propose that an impaired resolution of inflammation contributes to a chronic inflammatory state in MNGIE, potentially driving disease progression. Additionally, we suggest that the gut-liver axis plays a central role in MNGIE pathophysiology, with hepatic function being bidirectionally influenced by gut-derived factors.
dc.description.sponsorshipLily Foundation -- Purine Patients Metabolic Association [Bax_2023] -- [LILY-2017.18] -- This research was funded by the Lily Foundation, reference LILY-2017.18 and the Purine Patients Metabolic Association, reference Bax_2023.
dc.identifier.doi10.3390/ijms26189107
dc.identifier.issn1661-6596
dc.identifier.issn1422-0067
dc.identifier.issue18
dc.identifier.orcid0000-0001-9574-7841
dc.identifier.orcid0000-0001-6306-080X
dc.identifier.pmid41009664
dc.identifier.scopus2-s2.0-105017158410
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.3390/ijms26189107
dc.identifier.urihttps://hdl.handle.net/11454/134100
dc.identifier.volume26
dc.identifier.wosWOS:001580109300001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherMdpi
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20260922
dc.subjectMngie
dc.subjectMitochondrial Neurogastrointestinal Encephalomyopathy
dc.subjectMetabolomics
dc.subjectTymp
dc.subjectUntargeted Metabolomic Profiling
dc.subjectBiomarkers
dc.titleUntargeted Plasma Metabolomics Extends the Biomarker Profile of Mitochondrial Neurogastrointestinal Encephalomyopathy
dc.typeArticle

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