Hou Cheng-Cheng, Bao Hua-Fang, She Chun-Hui, Chen Hua-Yu, Pan Guan-Xing, Chen Hua-Ning, Rui Hong-Bing
Department of Rheumatology and Immunology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian, China.
Department of Rheumatology and Immunology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian, China.
Orphanet J Rare Dis. 2025 Jan 13;20(1):21. doi: 10.1186/s13023-024-03484-4.
Intestinal Behçet's syndrome (IBS) has high morbidity and mortality rates with serious complications. However, there are few specific biomarkers for IBS. The purposes of this study were to investigate the distinctive metabolic changes in plasma samples between IBS patients and healthy people, active IBS and inactive IBS patients, and to identify candidate metabolic biomarkers which would be useful for diagnosing and predicting IBS.
In this study, we performed a global untargeted metabolomics approach in plasma samples from 30 IBS patients and 20 healthy subjects. P value < 0.05 and variable importance projection (VIP) values > 1 were considered to be statistically significant metabolites. Univariate receiver operating characteristic (ROC) curve analysis was plotted as a measure for assessing the clinical performance of metabolites, and area under curve (AUC) were assessed.
A total of 147 differentially abundant metabolites (DAMs) were identified between IBS patients and normal control (NC) group. The potential pathways involved in the pathogenesis of IBS include linoleic acid metabolism; GABAergic synapse; biosynthesis of unsaturated fatty acids; valine, leucine and isoleucine biosynthesis; ovarian steroidogenesis; and others. In addition, a total of 103 significant metabolites were selected to distinguish active IBS from inactive IBS patients. Tyrosine metabolism, dopaminergic synapse and neuroactive ligand-receptor interaction were found to be closely related to the disease activity of IBS. Furthermore, three potential metabolites including quinate, stearidonic acid (SDA) and capric acid (CA) could significantly differ IBS patients from NC group. On the other hand, 1-methyladenosine (m1A), genipin, methylmalonic acid (MMA) and ascorbate could significantly differentiated active IBS from inactive IBS patients.
In conclusion, this study demonstrated the characteristic plasma metabolic profiles between IBS group and NC group, as well as between active and inactive IBS patients by using an untargeted LC/MS metabolomics profiling approach. In this study, quinate, SDA and CA were identified as potential diagnostic biomarkers for IBS. Additionally, m1A, genipin, MMA and ascorbate could serve as potential biomarkers for evaluating IBS activity. These findings might provide potential valuable insights for developing therapeutic strategies to manage IBS in the future.
肠道白塞病（IBS）发病率和死亡率高，并发症严重。然而，IBS的特异性生物标志物很少。本研究的目的是调查IBS患者与健康人、活动期IBS患者与非活动期IBS患者血浆样本中独特的代谢变化，并确定有助于诊断和预测IBS的候选代谢生物标志物。
在本研究中，我们对30例IBS患者和20名健康受试者的血浆样本进行了全面的非靶向代谢组学分析。P值<0.05且变量重要性投影（VIP）值>1被认为是具有统计学意义的代谢物。绘制单变量受试者工作特征（ROC）曲线作为评估代谢物临床性能的指标，并评估曲线下面积（AUC）。
在IBS患者与正常对照组（NC）之间共鉴定出147种差异丰富的代谢物（DAM）。IBS发病机制涉及的潜在途径包括亚油酸代谢；γ-氨基丁酸能突触；不饱和脂肪酸的生物合成；缬氨酸、亮氨酸和异亮氨酸的生物合成；卵巢甾体生成等。此外，共选择了103种显著代谢物以区分活动期IBS患者与非活动期IBS患者。发现酪氨酸代谢、多巴胺能突触和神经活性配体-受体相互作用与IBS的疾病活动密切相关。此外，三种潜在代谢物，包括奎尼酸、硬脂酸（SDA）和癸酸（CA），可使IBS患者与NC组显著不同。另一方面，1-甲基腺苷（m1A）、京尼平、甲基丙二酸（MMA）和抗坏血酸可显著区分活动期IBS患者与非活动期IBS患者。
总之，本研究通过非靶向LC/MS代谢组学分析方法展示了IBS组与NC组之间以及活动期和非活动期IBS患者之间的特征性血浆代谢谱。在本研究中，奎尼酸、SDA和CA被确定为IBS的潜在诊断生物标志物。此外，m1A、京尼平、MMA和抗坏血酸可作为评估IBS活动的潜在生物标志物。这些发现可能为未来制定治疗IBS的策略提供潜在的有价值的见解。
