Caterino M, Costanzo M, Castaldo A, Iacotucci P, Carnovale V, Ruoppolo M, Gelzo M, Castaldo G
CEINGE-Biotecnologie avanzate Franco Salvatore, Via G. Salvatore 486, Naples, 80145, Italy.
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy.
Sci Rep. 2025 Jan 2;15(1):479. doi: 10.1038/s41598-024-84191-9.
The development of targeted therapies that correct the effect of mutations in patients with cystic fibrosis (CF) and the relevant heterogeneity of the clinical expression of the disease require biomarkers correlated to the severity of the disease useful for monitoring the therapeutic effects. We applied a targeted metabolomic approach by LC-MS/MS on saliva samples from 70 adult CF patients and 63 age/sex-matched controls to investigate alterations in metabolic pathways related to pancreatic insufficiency (PI), Pseudomonas aeruginosa (PA) colonization, CF liver disease (CFLD), and CF related diabetes (CFRD). Sixty salivary metabolites were differentially expressed, with 11 being less abundant and 49 more abundant in CF patients. Among these, the most relevant alterations involved salivary ADMA, N-acetylornithine, methionine and methionine sulfoxide levels. Furthermore, methionine was significantly lower in CF patients with PI and salivary histamine levels were significantly lower in patients colonized by PA. Moreover, ADMA as well as N-acetylornithine and methionine were significantly lower in CF patients with CFRD than in patients without CFRD. Finally, the levels of DOPA resulted significantly lower in saliva from patients with liver disease. Our study revealed an imbalance in arginine methylation and tryptophan pathway related to CFRD and PI as well as alterations in dopaminergic pathway and Krebs cycle related to CFLD. This study also highlights different salivary metabolites as new potential biomarkers in a non-invasive sample that could represent a useful tool for the stratification and management of CF patients.
开发能够纠正囊性纤维化（CF）患者突变影响的靶向疗法以及该疾病临床表型的相关异质性，需要与疾病严重程度相关的生物标志物来监测治疗效果。我们采用液相色谱-串联质谱（LC-MS/MS）靶向代谢组学方法，对70例成年CF患者和63例年龄/性别匹配的对照者的唾液样本进行研究，以探究与胰腺功能不全（PI）、铜绿假单胞菌（PA）定植、CF肝病（CFLD）和CF相关糖尿病（CFRD）相关的代谢途径改变。60种唾液代谢物存在差异表达，其中11种在CF患者中含量较低，49种含量较高。其中，最相关的改变涉及唾液中不对称二甲基精氨酸（ADMA）、N-乙酰鸟氨酸、蛋氨酸和蛋氨酸亚砜水平。此外，PI型CF患者的蛋氨酸水平显著降低，PA定植患者的唾液组胺水平显著降低。此外，CFRD型CF患者的ADMA以及N-乙酰鸟氨酸和蛋氨酸水平显著低于无CFRD的患者。最后，肝病患者唾液中的多巴（DOPA）水平显著降低。我们的研究揭示了与CFRD和PI相关的精氨酸甲基化和色氨酸途径失衡，以及与CFLD相关的多巴胺能途径和三羧酸循环改变。这项研究还强调了不同的唾液代谢物作为非侵入性样本中的新潜在生物标志物，可能成为CF患者分层和管理的有用工具。
