Li Mingxiao, Zhang Rui, Xin Mingjie, Xu Yi, Liu Shijia, Yu Boyang, Zhang Boli, Liu Jihua
Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Department of Pharmacy, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.
Metabolites. 2022 Oct 20;12(10):997. doi: 10.3390/metabo12100997.
Ulcerative colitis is a type of non-specific inflammatory bowel disease with unclear etiology. It is considered a progressive disease with risks of bowel motility disorders, anorectal dysfunction, and even colorectal cancer. Commonly used diagnostic markers have poor specificity and cannot predict the development of ulcerative colitis. In this study, 77 serum samples (31 patients, 46 healthy controls) were analyzed using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry and 31 metabolites with significant level changes were found, revealing the relationship of ulcerative colitis to disturbed glutathione metabolism and caffeine metabolism. In addition, pyroglutamic acid, a biomarker of cervical cancer and gastric cancer, was identified with elevated levels in the serum of ulcerative colitis patients. The role of pyroglutamic acid was further analyzed, and the results indicated its positive correlation with the upregulation of inflammatory factors and increased levels of phosphorylated histone H2AX (H2AX) in IEC-6 cells, which are related to DNA damage. All these results suggest that pyroglutamic acid is not only a biomarker for distinguishing ulcerative colitis status, but that it is also a potential effective metabolite that promotes the transformation of ulcerative colitis to colorectal cancer.
溃疡性结肠炎是一种病因不明的非特异性炎症性肠病。它被认为是一种进展性疾病，存在肠道运动障碍、肛肠功能障碍甚至结直肠癌的风险。常用的诊断标志物特异性较差，无法预测溃疡性结肠炎的发展。在本研究中，使用高效液相色谱-四极杆飞行时间质谱法分析了77份血清样本（31例患者，46例健康对照），发现31种代谢物水平有显著变化，揭示了溃疡性结肠炎与谷胱甘肽代谢和咖啡因代谢紊乱的关系。此外，焦谷氨酸作为宫颈癌和胃癌的生物标志物，在溃疡性结肠炎患者血清中水平升高。进一步分析了焦谷氨酸的作用，结果表明其与炎症因子上调以及IEC-6细胞中与DNA损伤相关的磷酸化组蛋白H2AX（H2AX）水平升高呈正相关。所有这些结果表明，焦谷氨酸不仅是区分溃疡性结肠炎状态的生物标志物，而且是促进溃疡性结肠炎向结直肠癌转变的潜在有效代谢物。
