Department of Chemistry, Capital Normal University, No. 105, Xisanhuanbeilu, Haidian District, Beijing 100048, PR China.
Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 11, North Third Ring Road, Chaoyang District, Beijing 100029, PR China.
J Pharm Biomed Anal. 2021 Nov 30;206:114369. doi: 10.1016/j.jpba.2021.114369. Epub 2021 Sep 15.
Gastroesophageal reflux disease (GERD) is a common, chronic and complex upper gastrointestinal disease. In Traditional Chinese medicine (TCM) theory, GERD is classified into two main types: stagnant heat of liver and stomach (SHLS) and deficient cold of spleen and stomach (DCSS). The discovery and evaluation of potential biomarkers for different syndrome types of GERD may contribute to comprehend specific molecular mechanism and identify new targets for diagnosis and appropriate management. In our study, 60 subjects including 40 GERD patients (20 SHLS and 20 DCSS) and 20 healthy controls were recruited, and the serum and urine metabolic profiles from untargeted liquid chromatography coupled to mass spectrometry (LC-MS) metabolomics approach were obtained. Finally 38 biomarkers associated with disease were identified and 9 metabolic pathways were enriched. The most enriched pathways were amino acid metabolism, steroid hormone biosynthesis, glycerophospholipid metabolism, sphingolipid metabolism and TCA cycle. According to the area under curve (AUC) value, we propose a cohort of three metabolites from urine and serum samples as promising biomarkers for TCM syndrome differentiation of GERD, which are prolylhydroxyproline, glycitein-4'-O-glucuronide, capsianoside I in urine and neuAcalpha2-3Galbeta-Cer (d18:1/16:0), sphinganine, arachidonic acid in serum. The cumulative AUC value of merged biomarkers in urine and serum was 0.979 (95%CI 0.927-1) and 0.842 (95%CI 0.704-0.980), respectively. The results indicated that LC-MS based metabolomic profiling method might be an effective and promising tool on further pathogenesis discovering of GERD. The findings provided new strategy for the diagnosis of GERD TCM syndrome differentiation in clinic.
胃食管反流病（GERD）是一种常见的慢性上消化道疾病。在中医理论中，GERD 分为两种主要类型：肝胃郁热（SHLS）和脾胃虚寒（DCSS）。发现和评估 GERD 不同证型的潜在生物标志物可能有助于理解特定的分子机制，并为诊断和适当治疗确定新的靶点。在我们的研究中，共招募了 60 名受试者，包括 40 名 GERD 患者（20 名 SHLS 和 20 名 DCSS）和 20 名健康对照者，并采用非靶向液相色谱-质谱联用（LC-MS）代谢组学方法获得血清和尿液代谢谱。最终鉴定出 38 个与疾病相关的生物标志物，并富集了 9 个代谢途径。最富集的途径是氨基酸代谢、类固醇激素生物合成、甘油磷脂代谢、鞘脂代谢和 TCA 循环。根据曲线下面积（AUC）值，我们提出了一组来自尿液和血清样本的三种代谢物作为 GERD 中医证候鉴别有前途的生物标志物，分别为脯氨酰羟脯氨酸、黄豆苷元-4'-O-葡萄糖醛酸苷、尿中姜酮 I 和神经节苷脂（d18:1/16:0）、神经酰胺、血清中的花生四烯酸。尿液和血清中合并生物标志物的累积 AUC 值分别为 0.979（95%CI 0.927-1）和 0.842（95%CI 0.704-0.980）。结果表明，基于 LC-MS 的代谢组学分析方法可能是进一步研究 GERD 发病机制的有效而有前途的工具。这些发现为 GERD 中医证候鉴别诊断提供了新策略。
