Chojnowski Karol, Opiełka Mikołaj, Urbanowicz Krzysztof, Zawadzka Marta, Wangin Karolina, Smoleński Ryszard Tomasz, Mazurkiewicz-Bełdzińska Maria
Department of Developmental Neurology, Medical University of Gdansk, Gdansk, 80-211, Poland.
Department of Biochemistry, Medical University of Gdansk, Gdansk, 80-211, Poland.
Sci Rep. 2025 Apr 30;15(1):15262. doi: 10.1038/s41598-025-99805-z.
The biochemical processes of childhood-onset epilepsy remain unclear, with no reliable biomarkers for prognosis or management. Untargeted plasma metabolomics offers a valuable approach to uncover underlying pathomechanisms and identify actionable biomarkers. In this study, plasma samples from 18 pediatric patients with epilepsy and 11 age-matched healthy controls were analyzed using liquid chromatography-mass spectrometry. Data were analyzed using univariate and multivariate statistical methods and pathway enrichment analysis. Multivariate analyses demonstrated separation between the patient and control groups. A total of 19 endogenous metabolites (VIP > 1, adjusted p < 0.05) emerged as key differentiators. Compared with controls, patients exhibited significant reductions in tryptophan (Trp), 5-Hydroxyindoleacetic acid (5-HIAA), several gut microbiota-derived metabolites, including indole, indoxyl sulfate, and p-cresyl sulfate, as well as in niacin metabolism end-products - N1-Methyl-2-pyridone-5-carboxamide (Met2PY) and N1-Methyl-4-pyridone-3-carboxamide (Met4PY). In addition, patients showed decreased levels of tricarboxylic acid (TCA) cycle intermediates, concomitant with an increase in fatty acid derivatives and N-acetylneuraminic acid (Neu5Ac). The most substantially altered metabolic pathways in epilepsy patients involved the TCA cycle, vitamin A and C metabolism, prostaglandin synthesis, and D4/E4-neuroprostane formation. Observed alterations in tryptophan and microbiota-derived metabolites suggest gut dysbiosis may contribute to epilepsy development through the gut-brain axis. Moreover, the circulatory metabolic markers indicating an energy deficit and oxidative stress underscore the systemic impact of seizure activity.
儿童期癫痫的生化过程仍不清楚，尚无用于预后或治疗的可靠生物标志物。非靶向血浆代谢组学为揭示潜在的发病机制和识别可用于治疗的生物标志物提供了一种有价值的方法。在本研究中，使用液相色谱-质谱法分析了18例癫痫患儿和11例年龄匹配的健康对照者的血浆样本。采用单变量和多变量统计方法以及通路富集分析对数据进行分析。多变量分析显示患者组和对照组之间存在分离。共有19种内源性代谢物（VIP>1，校正p<0.05）成为关键差异物。与对照组相比，患者的色氨酸（Trp）、5-羟吲哚乙酸（5-HIAA）、几种肠道微生物群衍生的代谢物（包括吲哚、硫酸吲哚酚和对甲酚硫酸盐）以及烟酸代谢终产物——N1-甲基-2-吡啶酮-5-甲酰胺（Met2PY）和N1-甲基-4-吡啶酮-3-甲酰胺（Met4PY）显著降低。此外，患者的三羧酸（TCA）循环中间体水平降低，同时脂肪酸衍生物和N-乙酰神经氨酸（Neu5Ac）增加。癫痫患者中变化最显著的代谢途径涉及TCA循环、维生素A和C代谢、前列腺素合成以及D4/E4-神经前列腺素的形成。观察到的色氨酸和微生物群衍生代谢物的变化表明，肠道菌群失调可能通过肠-脑轴导致癫痫发展。此外，表明能量缺乏和氧化应激的循环代谢标志物强调了癫痫发作活动的全身影响。
