对人血浆的多组学分析揭示了儿童支原体肺炎中与炎症相关的色氨酸代谢重编程。
Multi-omics analysis of human plasma reveals reprogramming of tryptophan metabolism associated with inflammation in Mycoplasma pneumoniae pneumonia in children.
作者信息
Tang Yuyi, Fu Xian, Li Xiangyu, Fang Heping, Yang Fuping, Wang Run, Yin Hou-Hua, Chen Xue, Ren Luo, Zang Na, Zhong Wen, Chen Dapeng, Deng Yu, Liu Jun-Yan, Liu Enmei
机构信息
Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, China.
Center for Novel Target and Therapeutic Intervention, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China; Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, Chongqing 400016, China.
出版信息
J Infect. 2025 Jul;91(1):106525. doi: 10.1016/j.jinf.2025.106525. Epub 2025 May 31.
OBJECTIVES
Mycoplasma pneumoniae pneumonia (MPP) poses a severe threat to the health of children, yet its molecular alterations and pathogenic mechanisms remain poorly understood. In this study, we performed a multi-omics analysis to investigate the interactions between Mycoplasma pneumoniae and the pediatric host.
METHODS
We enrolled children with MPP and healthy controls (HC), constructing two independent cohorts. Plasma samples were analyzed using untargeted metabolomics and Olink proteomics to identify key metabolites and associated pathways. Targeted metabolomics was applied to validate and quantify metabolites within the most affected pathway. Correlation analyses were conducted between metabolites, cytokines, and clinical parameters.
RESULTS
Dysregulation of amino acid, lipid, and carbohydrate metabolism was observed in MPP patients compared with HC. Among these, tryptophan metabolism was the most prominently affected pathway. The rate-limiting enzyme indoleamine 2,3-dioxygenase 1 significantly increased across HC, general MPP (GMPP), and severe MPP (SMPP). Targeted metabolomics analysis in both cohorts verified the reprogramming of tryptophan metabolism, with reduced tryptophan levels, increased kynurenine metabolites, and decreased indole derivatives. Correlation analysis revealed broad and strong associations of these metabolites with cytokines (e.g., IFN-γ, CXCL10, IL-6, TNFSF/TNFRSF) and clinical parameters (e.g., CRP, PCT, LDH, D-Dimer). Furthermore, reductions in indole derivatives were also observed between SMPP and GMPP.
CONCLUSIONS
The reprogramming of tryptophan metabolism in pediatric MPP patients is characterized by upregulated kynurenine pathway and downregulated indole pathway, with potential regulatory crosstalk with inflammation. Our findings provide evidence for the role of tryptophan metabolism in MPP, highlighting its potential as novel therapeutic targets.
目的
肺炎支原体肺炎（MPP）对儿童健康构成严重威胁，但其分子改变和致病机制仍知之甚少。在本研究中，我们进行了多组学分析，以研究肺炎支原体与儿科宿主之间的相互作用。
方法
我们纳入了MPP患儿和健康对照（HC），构建了两个独立队列。使用非靶向代谢组学和Olink蛋白质组学分析血浆样本，以鉴定关键代谢物和相关途径。应用靶向代谢组学来验证和定量受影响最严重途径中的代谢物。对代谢物、细胞因子和临床参数进行相关性分析。
结果
与HC相比，MPP患者的氨基酸、脂质和碳水化合物代谢失调。其中，色氨酸代谢是受影响最显著的途径。在HC、普通MPP（GMPP）和重症MPP（SMPP）中，限速酶吲哚胺2,3-双加氧酶1均显著增加。两个队列中的靶向代谢组学分析均证实了色氨酸代谢的重编程，色氨酸水平降低，犬尿氨酸代谢物增加，吲哚衍生物减少。相关性分析显示，这些代谢物与细胞因子（如IFN-γ、CXCL10、IL-6、TNFSF/TNFRSF）和临床参数（如CRP、PCT、LDH、D-二聚体）存在广泛且强烈的关联。此外，SMPP和GMPP之间的吲哚衍生物也有所减少。
结论
儿科MPP患者色氨酸代谢的重编程表现为犬尿氨酸途径上调和吲哚途径下调，并与炎症存在潜在的调节性相互作用。我们的研究结果为色氨酸代谢在MPP中的作用提供了证据，突出了其作为新型治疗靶点的潜力。
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