Multi-omics approaches reveal the molecular mechanisms underlying the interaction between Clonorchis sinensis and mouse liver

Front Cell Infect Microbiol. 2023 Nov 24:13:1286977. doi: 10.3389/fcimb.2023.1286977. eCollection 2023.

Abstract

Introduction: Clonorchiasis remains a serious global public health problem, causing various hepatobiliary diseases. However, there is still a lack of overall understanding regarding the molecular events triggered by Clonorchis sinensis (C. sinensis) in the liver.

Methods: BALB/c mouse models infected with C. sinensis for 5, 10, 15, and 20 weeks were constructed. Liver pathology staining and observation were conducted to evaluate histopathology. The levels of biochemical enzymes, blood routine indices, and cytokines in the blood were determined. Furthermore, alterations in the transcriptome, proteome, and metabolome of mouse livers infected for 5 weeks were analyzed using multi-omics techniques.

Results: The results of this study indicated that adult C. sinensis can cause hepatosplenomegaly and liver damage, with the most severe symptoms observed at 5 weeks post-infection. However, as the infection persisted, the Th2 immune response increased and symptoms were relieved. Multi-omics analysis of liver infected for 5 weeks identified 191, 402 and 232 differentially expressed genes (DEGs), proteins (DEPs) and metabolites (DEMs), respectively. Both DEGs and DEPs were significantly enriched in liver fibrosis-related pathways such as ECM-receptor interaction and cell adhesion molecules. Key molecules associated with liver fibrosis and inflammation (Cd34, Epcam, S100a6, Fhl2, Itgax, and Retnlg) were up-regulated at both the gene and protein levels. The top three metabolic pathways, namely purine metabolism, arachidonic acid metabolism, and ABC transporters, were associated with liver cirrhosis, fibrosis, and cholestasis, respectively. Furthermore, metabolites that can promote liver inflammation and fibrosis, such as LysoPC(P-16:0/0:0), 20-COOH-leukotriene E4, and 14,15-DiHETrE, were significantly up-regulated.

Conclusion: Our study revealed that the most severe symptoms in mice infected with C. sinensis occurred at 5 weeks post-infection. Moreover, multi-omics analysis uncovered predominant molecular events related to fibrosis changes in the liver. This study not only enhances our understanding of clonorchiasis progression but also provides valuable insights into the molecular-level interaction mechanism between C. sinensis and its host liver.

Keywords: Clonorchis sinensis; metabolomics; molecular mechanisms; mouse liver; proteomics; transcriptomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Clonorchiasis* / pathology
  • Clonorchis sinensis* / genetics
  • Fibrosis
  • Liver / pathology
  • Liver Cirrhosis / pathology
  • Mice
  • Mice, Inbred BALB C
  • Multiomics

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (Grant No. 31900681), Guangxi Natural Science Foundation (Grant No. 2023GXNSFAA026201), Guangxi Natural Science Foundation (Grant No. 2018GXNSFBA050070), and Doctoral research start-up fund of Guangxi University of Chinese Medicine (Grant No. 2018BS015).