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...

Full description

Bibliographic Details
Main Authors: Simon Bos, Triana Lobatón, Martine De Vos, Sophie Van Welden, Vera Plekhova, Ellen De Paepe, Lynn Vanhaecke, Debby Laukens
Format: Article
Language:English
Published: Nature Portfolio 2023-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-50461-1
_version_ 1797371155029426176
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.
first_indexed 2024-03-08T18:15:42Z
format Article
id doaj.art-8ddd6d616e8540bea3c3272570b830b2
institution Directory Open Access Journal
issn 2045-2322
language English
last_indexed 2024-03-08T18:15:42Z
publishDate 2023-12-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
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
work_keys_str_mv AT simonbos acomprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease
AT trianalobaton acomprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease
AT martinedevos acomprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease
AT sophievanwelden acomprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease
AT veraplekhova acomprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease
AT ellendepaepe acomprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease
AT lynnvanhaecke acomprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease
AT debbylaukens acomprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease
AT simonbos comprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease
AT trianalobaton comprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease
AT martinedevos comprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease
AT sophievanwelden comprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease
AT veraplekhova comprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease
AT ellendepaepe comprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease
AT lynnvanhaecke comprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease
AT debbylaukens comprehensivemetabolitefingerprintoffibrostenosisinpatientswithcrohnsdisease