Perturbations of Metabolomic Profiling of Spleen From Rats Infected With Clonorchis sinensis Determined by LC-MS/MS Method

Zhang, Xiaoli; Hu, Xinyi; Chen, Rui; Sun, Baozhi; Gao, Yannan; Duan, Shanshan; Liu, Liyan; Han, Seung-Beom

doi:10.3389/fmolb.2020.561641

Cited by 10 publications

(6 citation statements)

References 51 publications

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“…Metabolomics has been employed to profile the metabolic alterations of parasitic diseases, including Schistosoma japonicum (S. japonicum) and Opisthorchis felineus in rodent models (Kokova et al, 2020;Qian et al, 2020). Similarly, we also found the changes of spleen metabolites and regulatory pathways during clonorchiasis (Zhang et al, 2020). Metabolomics contributes to supply dynamic alteration and explore the molecular mechanisms in these diseases (Yu et al, 2020).…”

Section: Introductionsupporting

confidence: 57%

Serum metabolic profiling of rats infected with Clonorchis sinensis using LC-MS/MS method

Han

Zhang²,

Ding³

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundClonorchiasis is an important foodborne parasitic disease. The omics-based-techniques could illuminate parasite biology and further make innovations in the research for parasitic diseases. However, knowledge about the serum metabolic profiles and related metabolic pathways in clonorchiasis is very limited.MethodsA untargeted ultra-high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) was used to profile the serum metabolites of rats at both 4 and 8 weeks post infection (wpi) with Clonorchis sinensis (C. sinensis). Additionally, multivariate statistical analysis methods were employed to identify differential metabolites. Next, serum amino acids and phosphatidylcholines (PCs) levels were determined by targeted metabolomics analysis.ResultA total of 10530 and 6560 ions were identified in ESI+ and ESI− modes. The levels of phosphatidylcholines, glycerophosphocholine and choline were significantly changed, with the shift in lipid metabolism. Significant changes were also observed in amino acids (isoleucine, valine, leucine, threonine, glutamate and glutamine). Targeted analysis showed that BCAAs (isoleucine, valine, leucine) levels significantly increased at 4 wpi and decreased at 8 wpi; threonine was increased at 8 wpi, whereas glutamate and glutamine showed a decreasing trend at 8 wpi. Additionally, the level of 17 PCs were significantly changed in infected rats. Marked metabolic pathways were involved in clonorchiasis, including glycerophospholipid metabolism, alanine, aspartate and glutamate metabolism, histidine metabolism and pyrimidine metabolism.ConclusionThese results show that C. sinensis infection can cause significant changes in the rat serum metabolism, especially in amino acids and lipids. The metabolic signature together with perturbations in metabolic pathways could provide more in depth understanding of clonorchiasis and further make potential therapeutic interventions.

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Section: Introductionsupporting

confidence: 57%

Serum metabolic profiling of rats infected with Clonorchis sinensis using LC-MS/MS method

Han

Zhang²,

Ding³

et al. 2023

Front. Cell. Infect. Microbiol.

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“…Several studies have suggested that the levels and metabolism of amino acids are intimately associated with parasitic growth and the development of diseases ( Muxel et al., 2019 ; Li et al., 2020 ). In our earlier research, the alteration of amino acid metabolism was observed in rat spleen and serum infected with C. sinensis ( Zhang et al., 2020 ; Han et al., 2023 ). In addition, Qiu et al.…”

Section: Discussionmentioning

confidence: 95%

Comparative analysis of bile metabolic profile in patients with biliary obstruction complicated by Clonorchis sinensis infection

Zhang,

Han,

Jiang

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundClonorchiasis is an important foodborne parasitic disease. However, eggs of Clonorchis sinensis (C. sinensis) cannot be detected in feces during biliary obstruction. Moreover, many diseases can cause biliary obstruction, such as gallstones, adenocarcinoma, cholangiocarcinoma and Ascaris lumbricoides infection. Therefore, it is of great significance to distinguish between patients of biliary obstruction and biliary obstruction with C. sinensis infection.MethodsA total of 48 biliary obstruction patients were enrolled, including 23 infected with C. sinensis (C. sinensis) (OB+C.s) and 25 non-infected subjects (OB). The bile samples were collected by endoscopic retrograde cholangiopancreatography and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). Additionally, multivariate statistical analysis methods were employed to identify differential metabolites. Next, bile amino acid levels were determined by targeted metabolomics analysis.ResultA total of 146 and 132 significant metabolites were identified in electrospray ionization (ESI)+ and ESI− modes, respectively. The levels of amino acids (asparagine, glutamate, ornithine) and polyamines (spermidine and spermine) were significantly changed. Targeted analysis showed that the levels of amino acids (such as L-arginine, L-glutamine, L-lysine, L-propionic, and L-tyrosine) were lower in OB+C.s patients compared to those in OB patients. Marked metabolic pathways were involved in “Glutathione metabolism”, “Caffeine metabolism”, “Alanine, aspartate and glutamate metabolism”, “Arginine and proline metabolism”, “Purine metabolism”, “Beta-Alanine metabolism”, and “D-glutamine and D-glutamate metabolism”.ConclusionThese results show that there were significant differences between OB+C.s and OB patients, especially in amino acids. The metabolic signature and perturbations in metabolic pathways may help to better distinguish OB+C.s and OB patients.

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“…Although studies have focused on the diagnosis, epidemiology, pathological mechanism, treatment, and vaccination for the disease [ 4 ], the diagnostic markers and molecular mechanisms remain poorly understood. Omics play an important role in screening the diagnostic markers of differential genes, proteins, and metabolites; the development of drug and vaccine targets; and elucidating the pathogenesis [ 10 – 12 ]. Metabolomics is a post-genomic discipline for studying the metabolome, and it can specifically reflect the real-time status of an organism, which makes it an optimal “readout” for external stimuli [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…Ghosh et al demonstrated the possibility of differentiating and identifying animals with cerebral malaria at an early pre-clinical stage based on serum metabolite profiles [ 14 ]. A non-targeted metabolomics approach has been shown to reveal the perturbations of spleen metabolism in clonorchiasis cases [ 12 ]. However, an effective and noninvasive biomarker has not been reported for the diagnosis of C. sinensis infections yet.…”

Section: Introductionmentioning

confidence: 99%

Multiple biochemical indices and metabolomics of Clonorchis sinensis provide a novel interpretation of biomarkers

et al. 2022

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Background Clonorchiasis, an infectious disease caused by the liver fluke Clonorchis sinensis, may lead to the development of liver and gallbladder diseases, and even cholangiocarcinoma (CCA). However, the pathogenesis, host-pathogen interaction, and diagnostic markers for clonorchiasis remain unclear. Methods Eighteen rabbits were randomly divided into control group (n = 9) and C. sinensis-infected group (n = 9), and their plasma samples were collected at 7, 14, 28, and 63 days post-infection (dpi). Biochemical indices and metabolites in different infection periods were detected. A non-targeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach was employed to investigate the metabolic profiles of plasma in rabbits, and related metabolic pathways of differential metabolites and correlation between candidate biochemical indices and differential metabolites were analyzed. Finally, the candidate biomarkers were verified with human samples using a targeted metabolomics method. Results The result of biochemical indices indicated C. sinensis infection would affect the liver function biochemical indices, especially alanine aminotransferase, aspartate transaminase (AST), glutamyl transpeptidase (GGT), total bile acid, high-density lipoprotein, and cholinesterase. The metabonomic results showed that 58, 212, 23, and 21 differential metabolites were identified in different phases of the infection. Multivariate statistical analysis of differential metabolites revealed distinct metabolic signatures during different phases of infection, with most of these signatures being observed at 14 dpi, which mainly influences the amino acid metabolisms. For metabolites and biochemical indices, AST, GGT, hypoxanthine, l-pipecolic acid, and d-glucuronate represented potential noninvasive biomarkers for the diagnosis of C. sinensis (P < 0.05 and AUC > 0.8). Furthermore, GGT and d-glucuronate levels were positively correlated with the infection (r(28) = 0.98, P < 0.0001) and showed excellent diagnostic performance (AUC = 0.972; 95% confidence interval, 0.921 to 1.000). Conclusions The present results provide new insights into plasma metabolic changes in rabbits during C. sinensis infection, and the potential biomarker may be used for developing an effective method to diagnose clonorchiasis in the future. Graphical Abstract

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Perturbations of Metabolomic Profiling of Spleen From Rats Infected With Clonorchis sinensis Determined by LC-MS/MS Method

Cited by 10 publications

References 51 publications

Serum metabolic profiling of rats infected with Clonorchis sinensis using LC-MS/MS method

Serum metabolic profiling of rats infected with Clonorchis sinensis using LC-MS/MS method

Comparative analysis of bile metabolic profile in patients with biliary obstruction complicated by Clonorchis sinensis infection

Multiple biochemical indices and metabolomics of Clonorchis sinensis provide a novel interpretation of biomarkers

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