Multi-omics reveals the impact of Clonorchis sinensis infection on mouse gut microbiota, metabolomics and transcriptomics

Clonorchiasis is a globally significant zoonotic disease. The complex interplay among gut microbiota, metabolomics, and host transcriptomics is increasingly recognized as a crucial factor in maintaining health. However, the impacts of Clonorchis sinensis (C. sinensis) infection on these interactions remain unclear. This study investigates the relationships and pathogenic mechanisms of C. sinensis infection using a BALB/c mouse model infected for 2–15 week post-infection (wpi). Fecal samples were collected at multiple time points to profile gut microbiota dynamics, while simultaneously detecting alterations in the ileal tissue transcriptome and fecal metabolome at 5 wpi. Gut microbiota analysis revealed that C. sinensis infection disrupted microbial homeostasis, significantly altering the Firmicutes/Bacteroidetes (F/B) ratio, with the most pronounced effects observed at 5 wpi. The impact on microbiota increased during the larval-to-adult transition (2–5 wpi) and diminished in the later adult stage (8–15 wpi). Transcriptomic analysis at 5 wpi revealed substantial dysregulation of immune- and metabolism-related genes. Functional enrichment analyses identified key GO terms of complement activation and immune response, and KEGG pathways of chemokine signaling and Th1/Th2 cell differentiation. Concurrent metabolomic profiling revealed significant changes in metabolites, including PC(18:0/0:0), 2-LysoPC, and LysoPC(18:0/0:0), enriched in multiple lipid metabolism pathways. Multi-omics correlation analysis demonstrated strong associations between specific bacterial genera (e.g., Lachnoclostridium, Turicibacter, Dubosiella and Marvinbryantia) and lipid metabolism, as well as metabolites and genes linked to the Lands cycle, suggesting these genera as keystone bridging microbial-immune-metabolic crosstalk. This study elucidates the dynamic changes in gut microbiota and multi-omics interactions during C. sinensis infection, providing a foundation for further mechanistic research and potential therapeutic targets.