Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria del Hospital de La Princesa, Universidad Autónoma de Madrid, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.
Precision Medicine and Metabolism Lab, CIC bioGUNE, Derio, Spain.
Inflamm Bowel Dis. 2024 Feb 1;30(2):167-182. doi: 10.1093/ibd/izad154.
Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation.
Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses.
A total of 137 Crohn's disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn's disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters.
This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.
炎症性肠病（IBD）是一种常见的慢性非治愈性疾病，与深刻的代谢变化有关。因此，发现用于阐明 IBD 发病机制以及诊断和预测 IBD 的新型分子指标至关重要。我们试图在开始治疗之前确定不同 IBD 亚组之间的独特代谢特征。
使用质子核磁共振波谱法对新诊断的未经治疗的 IBD 患者以及年龄和性别匹配的健康对照（HC）个体的血清和尿液样本进行了检测。基于单变量和多变量统计分析确定了代谢差异。
共纳入 137 例克罗恩病患者、202 例溃疡性结肠炎患者和 338 例 HC 个体。在 IBD 队列中，在每个亚组比较中都检测到了一些可区分的代谢物。大多数差异表明 IBD 患者的能量和氨基酸代谢发生了改变，机体对能量的需求主要通过酮体来满足。与 HC 个体相比，克罗恩病患者的代谢物差异比溃疡性结肠炎患者更为明显和多样，而且在血清中比在尿液中更为明显。此外，聚类分析显示，根据对患者临床、人体测量和代谢变量的分析，这 3 个亚组患者有 3 种不同的特征，且彼此之间有明显的差异。但是，在这 3 个聚类中没有发现相关的表型差异。
本研究强调了新诊断的未经治疗的 IBD 患者的不同亚组中存在的分子改变。这些患者的代谢组学特征可能进一步了解 IBD 亚组的发病机制。血清代谢组似乎对 IBD 的发作特别敏感。
