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A comprehensive metabolite fingerprint of fibrostenosis in patients with Crohn's disease.
Bos, Simon; Lobatón, Triana; De Vos, Martine; Van Welden, Sophie; Plekhova, Vera; De Paepe, Ellen; Vanhaecke, Lynn; Laukens, Debby.
Afiliación
  • Bos S; Department of Internal Medicine and Pediatrics, Ghent University, C. Heymanslaan 10, 0MRB2, 9000, Ghent, Belgium.
  • Lobatón T; VIB Center for Inflammation Research, Ghent, Belgium.
  • De Vos M; Department of Internal Medicine and Pediatrics, Ghent University, C. Heymanslaan 10, 0MRB2, 9000, Ghent, Belgium.
  • Van Welden S; Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium.
  • Plekhova V; Department of Internal Medicine and Pediatrics, Ghent University, C. Heymanslaan 10, 0MRB2, 9000, Ghent, Belgium.
  • De Paepe E; Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium.
  • Vanhaecke L; Department of Internal Medicine and Pediatrics, Ghent University, C. Heymanslaan 10, 0MRB2, 9000, Ghent, Belgium.
  • Laukens D; VIB Center for Inflammation Research, Ghent, Belgium.
Sci Rep ; 13(1): 23036, 2023 12 27.
Article en En | MEDLINE | ID: mdl-38155265
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Crohn Límite: Humans Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Crohn Límite: Humans Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido