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

Abstract

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

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

“…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. (2022) found that the amino acid levels in the serum of rabbits were altered after C. sinensis infection.…”

“…Additionally, a decrease in the quantity of extracellular glutamine makes cells more susceptible to apoptosis ( Chen and Cui, 2015 ). Studies have shown that the level of glutamine was significantly reduced in the serum of rabbits infected with C. sinensis ( Qiu et al., 2022 ). Therefore, we speculated that glutamate and glutamine may play important roles in distinguishing OB+C.s patients from OB patients.…”

A point-of-care testing assay for clonorchiasis using a EuNPs-CsTR1 fluorescent probe-based immunoassay

“…C . sinensis metacercariae were obtained from naturally infected Pseudorasbora parva purchased from endemic areas in Changchun city, Jilin Province, China, and were orally administered to New Zealand white rabbits [ 27 ]. Adult worms were collected from the bile ducts of infected rabbits 5 weeks post-infection.…”

Revealing the dynamic whole transcriptome landscape of Clonorchis sinensis: Insights into the regulatory roles of noncoding RNAs and microtubule-related genes in development

“…These results imply the crucial significance of transcriptome analysis in comprehending the survival strategies, respiratory processes, and metabolism of C . sinensis [ 11 ]. The differential gene expression and regulatory patterns across developmental stages and tissues provide valuable insights into the intricate biology of this parasite, thus providing information on potential targets for understanding its pathogenicity and for developing effective interventions.…”