Wu Xiao-Xia, Ban Wan-Li, Wu Li-Jiang, Qi Wen-Jing, Borhani Mehdi, He Xiao-Ying, Liu Xiao-Lei, Liu Ming-Yuan, Ding Jing
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis and College of Veterinary Medicine, Jilin University, Changchun, 130062, China.
National Animal Echinococcosis Reference Laboratory, Veterinary Research Institute of Xinjiang Academy of Animal Husbandry, Urumqi, 830010, China.
Parasit Vectors. 2024 Dec 30;17(1):547. doi: 10.1186/s13071-024-06599-6.
Echinococcosis is a zoonotic disease caused by an Echinococcus tapeworm infection. While diagnostic methods for humans often rely on ultrasound imaging and immunodiagnostic techniques, diagnosis in intermediate hosts typically has no widely used diagnostic markers, hampering disease control efforts.
The differences in serum metabolites of sheep infected with Echinococcus granulosus and a control group were analyzed using ultrahigh-performance liquid chromatography (UHPLC) separation with tandem mass spectrometry (MS/MS) detection. This provided a basis for the early diagnosis and pathogenetic study of cystic echinococcosis (CE) in intermediate hosts at the metabolomics level. Orthogonal projections to latent structures-discriminant analysis (OPLS-DA) were used to analyze different metabolites in the serum of the two groups. The differentially abundant metabolites were entered into the MetaboAnalyst 5.0 online analysis website for processing, and the top-15-ranked metabolic pathways were set to produce bubble plots and differential abundance score plots, with a significant difference of P < 0.05 and a false discovery rate (FDR) < 0.1 as the screening conditions.
Data analyses of serum samples from both groups identified a total of 1905 significantly different metabolites, where 841 metabolites were upregulated and 1064 metabolites were downregulated. Twelve metabolites were significantly upregulated and 21 metabolites were significantly downregulated in the experimental group. Then, the 1,7-dihydroxyxanthone, 2-methylbutyrylglycine, 3,3-dimethylglutaric acid, 5,12-dihydroxy-6,8,10,14,17-eicosapentaenoic acid, 9-hydroperoxy-10E,12Z,15Z-octadecatrienoic acid, and trimethylamine N-oxide 6 metabolites were selected as diagnostically valuable candidate biomarkers (area under the curve [AUC] > 0.7). These differential metabolites are involved in various metabolic pathways, including amino acid metabolites (arginine, L-isoleucine, L-valine) and fatty acid metabolism (fenugreek, arachidonic acid, linolenic acid). Compared with the control group, sheep in the CE group had increased serum levels of fenugreek acid, while all other metabolites such as glycine showed significantly reduced serum levels (P < 0.01).
Through non-targeted metabolomic analysis of the serum of CE-infected sheep, differential metabolites closely related to amino acid metabolism and the fatty acid metabolism pathway were identified. These differentially abundant metabolites can serve as biomarkers for diagnosing CE infection in intermediate sheep hosts.
棘球蚴病是一种由棘球绦虫感染引起的人畜共患病。虽然人类的诊断方法通常依赖于超声成像和免疫诊断技术，但中间宿主的诊断通常没有广泛使用的诊断标志物，这阻碍了疾病控制工作。
采用超高效液相色谱（UHPLC）分离结合串联质谱（MS/MS）检测，分析感染细粒棘球绦虫的绵羊与对照组血清代谢物的差异。这为在代谢组学水平上对中间宿主囊型棘球蚴病（CE）进行早期诊断和发病机制研究提供了依据。采用正交投影到潜在结构判别分析（OPLS-DA）分析两组血清中的不同代谢物。将差异丰富的代谢物输入MetaboAnalyst 5.0在线分析网站进行处理，设置排名前15的代谢途径以生成气泡图和差异丰度评分图，以P<0.05和错误发现率（FDR）<0.1的显著差异作为筛选条件。
两组血清样本的数据分析共鉴定出1905种显著不同的代谢物，其中841种代谢物上调，1064种代谢物下调。实验组中有12种代谢物显著上调，21种代谢物显著下调。然后，选择1,7-二羟基呫吨酮、2-甲基丁酰甘氨酸、3,3-二甲基戊二酸、5,12-二羟基-6,8,10,14,17-二十碳五烯酸、9-氢过氧-10E,12Z,15Z-十八碳三烯酸和氧化三甲胺6种代谢物作为具有诊断价值的候选生物标志物（曲线下面积[AUC]>0.7）。这些差异代谢物参与各种代谢途径，包括氨基酸代谢物（精氨酸、L-异亮氨酸、L-缬氨酸）和脂肪酸代谢（葫芦巴酸、花生四烯酸、亚麻酸）。与对照组相比，CE组绵羊血清中葫芦巴酸水平升高，而其他所有代谢物如甘氨酸的血清水平显著降低（P<0.01）。
通过对CE感染绵羊血清进行非靶向代谢组学分析，鉴定出与氨基酸代谢和脂肪酸代谢途径密切相关的差异代谢物。这些差异丰富的代谢物可作为诊断中间宿主绵羊CE感染的生物标志物。
