Identification of serum biomarkers for cystic echinococcosis in sheep through untargeted metabolomic analysis using LC–MS/MS technology

Abstract Background 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 dise...

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Main Authors: Xiao-Xia Wu, Wan-Li Ban, Li-Jiang Wu, Wen-Jing Qi, Mehdi Borhani, Xiao-Ying He, Xiao-Lei Liu, Ming-Yuan Liu, Jing Ding
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Parasites & Vectors
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Online Access:https://doi.org/10.1186/s13071-024-06599-6
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author Xiao-Xia Wu
Wan-Li Ban
Li-Jiang Wu
Wen-Jing Qi
Mehdi Borhani
Xiao-Ying He
Xiao-Lei Liu
Ming-Yuan Liu
Jing Ding
author_facet Xiao-Xia Wu
Wan-Li Ban
Li-Jiang Wu
Wen-Jing Qi
Mehdi Borhani
Xiao-Ying He
Xiao-Lei Liu
Ming-Yuan Liu
Jing Ding
author_sort Xiao-Xia Wu
collection DOAJ
description Abstract Background 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. Methods 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. Results 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). Conclusions 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. Graphical abstract
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spelling doaj-art-9589ce7522354bb2a79115a5f137ba982025-01-05T12:10:03ZengBMCParasites & Vectors1756-33052024-12-0117111410.1186/s13071-024-06599-6Identification of serum biomarkers for cystic echinococcosis in sheep through untargeted metabolomic analysis using LC–MS/MS technologyXiao-Xia Wu0Wan-Li Ban1Li-Jiang Wu2Wen-Jing Qi3Mehdi Borhani4Xiao-Ying He5Xiao-Lei Liu6Ming-Yuan Liu7Jing Ding8State 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 UniversityNational Animal Echinococcosis Reference Laboratory, Veterinary Research Institute of Xinjiang Academy of Animal HusbandryNational Animal Echinococcosis Reference Laboratory, Veterinary Research Institute of Xinjiang Academy of Animal HusbandryState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia First Affiliated Hospital of Xinjiang Medical UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityState 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 UniversityAbstract Background 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. Methods 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. Results 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). Conclusions 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. Graphical abstracthttps://doi.org/10.1186/s13071-024-06599-6Echinococcus granulosusSerumNon-targeted metabolomicsLC–MS/MSBiomarkers
spellingShingle Xiao-Xia Wu
Wan-Li Ban
Li-Jiang Wu
Wen-Jing Qi
Mehdi Borhani
Xiao-Ying He
Xiao-Lei Liu
Ming-Yuan Liu
Jing Ding
Identification of serum biomarkers for cystic echinococcosis in sheep through untargeted metabolomic analysis using LC–MS/MS technology
Parasites & Vectors
Echinococcus granulosus
Serum
Non-targeted metabolomics
LC–MS/MS
Biomarkers
title Identification of serum biomarkers for cystic echinococcosis in sheep through untargeted metabolomic analysis using LC–MS/MS technology
title_full Identification of serum biomarkers for cystic echinococcosis in sheep through untargeted metabolomic analysis using LC–MS/MS technology
title_fullStr Identification of serum biomarkers for cystic echinococcosis in sheep through untargeted metabolomic analysis using LC–MS/MS technology
title_full_unstemmed Identification of serum biomarkers for cystic echinococcosis in sheep through untargeted metabolomic analysis using LC–MS/MS technology
title_short Identification of serum biomarkers for cystic echinococcosis in sheep through untargeted metabolomic analysis using LC–MS/MS technology
title_sort identification of serum biomarkers for cystic echinococcosis in sheep through untargeted metabolomic analysis using lc ms ms technology
topic Echinococcus granulosus
Serum
Non-targeted metabolomics
LC–MS/MS
Biomarkers
url https://doi.org/10.1186/s13071-024-06599-6
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