Background The therapeutic challenges posed by nontuberculous mycobacterial pulmonary disease (NTM-PD) contribute to an unmet medical need. In this study, we aimed to investigate NTM-PD-specific metabolic pathways using serum metabolomics to understand disease pathogenesis. Methods Mass spectrometry-based untargeted metabolomic profiling of serum from patients with NTM-PD (n = 50), patients with bronchiectasis (n = 50), and healthy controls (n = 60) was performed. Selected metabolites were validated by an independent cohort and subjected to pathway analysis and classification modeling. Results Leucine, tyrosine, inosine, proline, 5-oxoproline, and hypoxanthine levels increased in the NTM-PD group compared with the healthy control group. Furthermore, levels of antioxidant metabolites (ferulic acid, α-lipoic acid, biotin, and 2,8-phenazinediamine) decreased in patients with NTM-PD. These changes were associated with arginine- and proline-related metabolism, leading to generation of reactive oxygen species. Interestingly, the observed metabolic changes in the NTM-PD group overlapped with those in the bronchiectasis group. Conclusion In NTM-PD, 11 metabolites linked to increased oxidative stress were significantly altered from those in healthy controls. Our findings enhance a comprehensive understanding of NTM-PD pathogenesis and provide insights for novel treatment approaches.

中文翻译：

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非结核分枝杆菌性肺部疾病的代谢组学特征

背景 非结核分枝杆菌肺病 (NTM-PD) 带来的治疗挑战导致医疗需求未得到满足。在本研究中，我们旨在利用血清代谢组学研究 NTM-PD 特异性代谢途径，以了解疾病发病机制。方法 对 NTM-PD 患者 (n = 50)、支气管扩张患者 (n = 50) 和健康对照 (n = 60) 的血清进行基于质谱的非靶向代谢组学分析。选定的代谢物由独立队列进行验证，并进行路径分析和分类建模。结果与健康对照组相比，NTM-PD组的亮氨酸、酪氨酸、肌苷、脯氨酸、5-氧代脯氨酸和次黄嘌呤水平升高。此外，NTM-PD 患者的抗氧化代谢物（阿魏酸、α-硫辛酸、生物素和 2,8-吩嗪二胺）水平降低。这些变化与精氨酸和脯氨酸相关的代谢有关，导致活性氧的产生。有趣的是，NTM-PD 组观察到的代谢变化与支气管扩张组的代谢变化重叠。结论 在 NTM-PD 中，与健康对照者相比，与氧化应激增加相关的 11 种代谢物发生了显着改变。我们的研究结果增强了对 NTM-PD 发病机制的全面了解，并为新的治疗方法提供了见解。