A comprehensive metabolite fingerprint of fibrostenosis in patients with Crohn’s disease
Abstract Intestinal fibrostenosis in patients with Crohn’s disease (CD) is a common and untreatable comorbidity that is notoriously difficult to monitor. We aimed to find metabolites associated with the presence of fibrostenosis in patients with CD using targeted and untargeted metabolomics analyses...
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Nature Portfolio
2023-12-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-023-50461-1 |
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author | Simon Bos Triana Lobatón Martine De Vos Sophie Van Welden Vera Plekhova Ellen De Paepe Lynn Vanhaecke Debby Laukens |
author_facet | Simon Bos Triana Lobatón Martine De Vos Sophie Van Welden Vera Plekhova Ellen De Paepe Lynn Vanhaecke Debby Laukens |
author_sort | Simon Bos |
collection | DOAJ |
description | Abstract Intestinal fibrostenosis in patients with Crohn’s disease (CD) is a common and untreatable comorbidity that is notoriously difficult to monitor. We aimed to find metabolites associated with the presence of fibrostenosis in patients with CD using targeted and untargeted metabolomics analyses of serum and primary cell cultures using hyphenated ultra-high performance liquid chromatography high-resolution mass spectrometry. Targeted metabolomics revealed 11 discriminating metabolites in serum, which were enriched within the arginine and proline metabolism pathway. Based on untargeted metabolomics and discriminant analysis, 166 components showed a high predictive value. In addition, human intestinal fibroblasts isolated from stenotic tissue were characterized by differential levels of medium-chain dicarboxylic acids, which are proposed as an energy source through beta-oxidation, when oxidative phosphorylation is insufficient. Another energy providing pathway in such situations is anaerobic glycolysis, a theory supported by increased expression of hexokinase 2 and solute carrier family 16 member 1 in stenotic fibroblasts. Of interest, four (unannotated) metabolic components showed a negative correlation with hexokinase 2 gene expression. Together, this study provides a discriminative metabolic fingerprint in the serum and in intestinal fibroblasts of stenotic and non-stenotic patients with CD suggestive for increased production of building blocks for collagen synthesis and increased glycolysis. |
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institution | Directory Open Access Journal |
issn | 2045-2322 |
language | English |
last_indexed | 2024-03-08T18:15:42Z |
publishDate | 2023-12-01 |
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spelling | doaj.art-8ddd6d616e8540bea3c3272570b830b22023-12-31T12:10:49ZengNature PortfolioScientific Reports2045-23222023-12-0113111110.1038/s41598-023-50461-1A comprehensive metabolite fingerprint of fibrostenosis in patients with Crohn’s diseaseSimon Bos0Triana Lobatón1Martine De Vos2Sophie Van Welden3Vera Plekhova4Ellen De Paepe5Lynn Vanhaecke6Debby Laukens7Department of Internal Medicine and Pediatrics, Ghent UniversityDepartment of Internal Medicine and Pediatrics, Ghent UniversityDepartment of Internal Medicine and Pediatrics, Ghent UniversityDepartment of Internal Medicine and Pediatrics, Ghent UniversityDepartment of Translational Physiology, Infectiology and Public Health, Ghent UniversityDepartment of Translational Physiology, Infectiology and Public Health, Ghent UniversityDepartment of Translational Physiology, Infectiology and Public Health, Ghent UniversityDepartment of Internal Medicine and Pediatrics, Ghent UniversityAbstract Intestinal fibrostenosis in patients with Crohn’s disease (CD) is a common and untreatable comorbidity that is notoriously difficult to monitor. We aimed to find metabolites associated with the presence of fibrostenosis in patients with CD using targeted and untargeted metabolomics analyses of serum and primary cell cultures using hyphenated ultra-high performance liquid chromatography high-resolution mass spectrometry. Targeted metabolomics revealed 11 discriminating metabolites in serum, which were enriched within the arginine and proline metabolism pathway. Based on untargeted metabolomics and discriminant analysis, 166 components showed a high predictive value. In addition, human intestinal fibroblasts isolated from stenotic tissue were characterized by differential levels of medium-chain dicarboxylic acids, which are proposed as an energy source through beta-oxidation, when oxidative phosphorylation is insufficient. Another energy providing pathway in such situations is anaerobic glycolysis, a theory supported by increased expression of hexokinase 2 and solute carrier family 16 member 1 in stenotic fibroblasts. Of interest, four (unannotated) metabolic components showed a negative correlation with hexokinase 2 gene expression. Together, this study provides a discriminative metabolic fingerprint in the serum and in intestinal fibroblasts of stenotic and non-stenotic patients with CD suggestive for increased production of building blocks for collagen synthesis and increased glycolysis.https://doi.org/10.1038/s41598-023-50461-1 |
spellingShingle | Simon Bos Triana Lobatón Martine De Vos Sophie Van Welden Vera Plekhova Ellen De Paepe Lynn Vanhaecke Debby Laukens A comprehensive metabolite fingerprint of fibrostenosis in patients with Crohn’s disease Scientific Reports |
title | A comprehensive metabolite fingerprint of fibrostenosis in patients with Crohn’s disease |
title_full | A comprehensive metabolite fingerprint of fibrostenosis in patients with Crohn’s disease |
title_fullStr | A comprehensive metabolite fingerprint of fibrostenosis in patients with Crohn’s disease |
title_full_unstemmed | A comprehensive metabolite fingerprint of fibrostenosis in patients with Crohn’s disease |
title_short | A comprehensive metabolite fingerprint of fibrostenosis in patients with Crohn’s disease |
title_sort | comprehensive metabolite fingerprint of fibrostenosis in patients with crohn s disease |
url | https://doi.org/10.1038/s41598-023-50461-1 |
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