Absolute quantitative lipidomics of Clonorchis sinensis-infected rats reveals key alterations in metabolic pathways

Clonorchis sinensis (C. sinensis) infection is a significant public health concern due to its association with chronic hepatobiliary diseases. However, the mechanisms underlying C. sinensis infection and its effects on host metabolism remain poorly understood. In this study, serum samples were collected from rats at 4 and 8 weeks post-infection (wpi), and lipid metabolites were analyzed using absolute quantitative lipidomics with UHPLC-MS/MS. Multivariate analyses were conducted to identify differentially expressed lipids, and pathway analysis was performed utilizing the MetaboAnalyst and KEGG databases. A total of 12 lipid subclasses across five major categories were identified, with triacylglycerols (TAG) being the most significantly affected. At 4 wpi, 230 lipids were up-regulated and 18 down-regulated, whereas at 8 wpi, 88 were up-regulated and 73 down-regulated compared to controls. The results revealed significant alterations in lipid profiles, particularly in TAG, free fatty acids (FFA), and phosphatidylcholine (PC), with phosphatidylethanolamine (PE) exhibiting the most pronounced dynamic changes. Pathway enrichment analysis revealed significant involvement of the biosynthesis of unsaturated fatty acids, alpha-linolenic acid metabolism, and glycerolipid metabolism in response to the infection. This study identifies significant alterations in the lipidomics of C. sinensis-infected rats, revealing critical perturbations in key metabolic pathways, which are likely involved in the host's immune and inflammatory responses. These findings not only offer potential therapeutic targets, but also deepen our understanding of host-parasite metabolic interactions during chronic infection.