Department of Human Anatomy, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
Department of Pathogenic Biology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
Parasit Vectors. 2023 Aug 30;16(1):304. doi: 10.1186/s13071-023-05881-3.
Leishmaniasis is one of the most neglected tropical diseases and is spread mainly in impoverished regions of the world. Although many studies have focused on the host's response to Leishmania invasion, relatively less is known about the complex processes at the metabolic level, especially the metabolic alterations in the infected hosts.
In this study, we conducted metabolomics analysis on the urine of golden hamsters in the presence or absence of visceral leishmaniasis (VL) using the ultra-performance liquid chromatography (UPLC) system tandem high-resolution mass spectrometer (HRMS). The metabolic characteristics of urine samples, along with the histopathological change and the parasite burden of liver and spleen tissues, were detected at 4 and 12 weeks post infection (WPI), respectively.
Amino acid metabolism was extensively affected at both stages of VL progression. Meanwhile, there were also distinct metabolic features at different stages. At 4 WPI, the significantly affected metabolic pathways involved alanine, aspartate and glutamate metabolism, the pentose phosphate pathway (PPP), histidine metabolism, tryptophan metabolism and tyrosine metabolism. At 12 WPI, the markedly enriched metabolic pathways were almost concentrated on amino acid metabolism, including tyrosine metabolism, taurine and hypotaurine metabolism and tryptophan metabolism. The dysregulated metabolites and metabolic pathways at 12 WPI were obviously less than those at 4 WPI. In addition, seven metabolites that were dysregulated at both stages through partial least squares-discriminant analysis (PLS-DA) and receiver-operating characteristic (ROC) tests were screened to be of diagnostic potential. The combination of these metabolites as a potential biomarker panel showed satisfactory performance in distinguishing infection groups from control groups as well as among different stages of infection.
Our findings could provide valuable information for further understanding of the host response to Leishmania infection from the aspect of the urine metabolome. The proposed urine biomarker panel could help in the development of a novel approach for the diagnosis and prognosis of VL.
利什曼病是最被忽视的热带病之一，主要分布在世界贫困地区。尽管许多研究集中在宿主对利什曼原虫入侵的反应上，但对代谢水平的复杂过程，特别是感染宿主的代谢变化，了解相对较少。
在本研究中，我们使用超高效液相色谱（UPLC）系统串联高分辨率质谱（HRMS）对存在或不存在内脏利什曼病（VL）的金黄地鼠尿液进行代谢组学分析。分别在感染后 4 周和 12 周（WPI）检测尿液样本的代谢特征、肝脾组织的组织病理学变化和寄生虫负担。
在 VL 进展的两个阶段，氨基酸代谢受到广泛影响。同时，在不同阶段也存在明显的代谢特征。在 4 WPI 时，受显著影响的代谢途径涉及丙氨酸、天冬氨酸和谷氨酸代谢、戊糖磷酸途径（PPP）、组氨酸代谢、色氨酸代谢和酪氨酸代谢。在 12 WPI 时，明显富集的代谢途径几乎集中在氨基酸代谢上，包括酪氨酸代谢、牛磺酸和次牛磺酸代谢和色氨酸代谢。与 4 WPI 相比，12 WPI 时失调的代谢物和代谢途径明显减少。此外，通过偏最小二乘判别分析（PLS-DA）和接收者操作特征（ROC）测试筛选出在两个阶段都失调的 7 种代谢物，具有诊断潜力。这些代谢物的组合作为一个潜在的生物标志物组合，在区分感染组和对照组以及不同感染阶段方面表现出令人满意的性能。
我们的研究结果可以为进一步从尿液代谢组学方面了解宿主对利什曼原虫感染的反应提供有价值的信息。所提出的尿液生物标志物组合可能有助于开发一种新的 VL 诊断和预后方法。
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