Department of Internal Medicine and Pediatrics, Ghent University, C. Heymanslaan 10, 0MRB2, 9000, Ghent, Belgium.
VIB Center for Inflammation Research, Ghent, Belgium.
Sci Rep. 2023 Dec 27;13(1):23036. doi: 10.1038/s41598-023-50461-1.
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.
克罗恩病（CD）患者的肠道纤维化是一种常见且无法治愈的并发症，其监测极具挑战性。我们旨在使用靶向和非靶向代谢组学分析血清和原代细胞培养物，通过连接的超高效液相色谱高分辨率质谱法，寻找与 CD 患者纤维化存在相关的代谢物。靶向代谢组学在血清中发现了 11 种具有区分能力的代谢物，这些代谢物富集在精氨酸和脯氨酸代谢途径中。基于非靶向代谢组学和判别分析，有 166 个成分显示出较高的预测价值。此外，从狭窄组织中分离出的人肠道成纤维细胞表现出中等链二羧酸的差异水平，这些二羧酸通过β氧化被提议作为能量来源，而当氧化磷酸化不足时。在这种情况下的另一种提供能量的途径是无氧糖酵解，这一理论得到了狭窄成纤维细胞中己糖激酶 2 和溶质载体家族 16 成员 1 表达增加的支持。有趣的是，有四个（未注释）代谢成分与己糖激酶 2 基因表达呈负相关。总的来说，这项研究在 CD 狭窄和非狭窄患者的血清和肠道成纤维细胞中提供了一个有区别的代谢指纹，提示胶原合成的构建块产生增加和糖酵解增加。
