Integrated multi-omics analyses of molecular pathways underlying microcystin-LR toxicity in the earthworm Eisenia...

Contamination of soil with microcystin-LR (MC-LR) has emerged as a significant environmental concern, but its toxicological impacts and underlying mechanisms on soil-dwelling invertebrates are not yet fully elucidated. Here we employed a comprehensive strategy integrating histopathological, ultrastructural, biochemical, and multi-omics (metabolomics and proteomics) analyses to investigate the effects of MC-LR on Eisenia fetida, a model soil organism. MC-LR exposure induced dose-dependent structural damage to the epidermal and intestinal tissues, disrupting antioxidant systems while elevating detoxification enzyme activity. Metabolomic profiling identified 93 significantly altered metabolites in the earthworms following exposure to MC-LR at a concentration of 0.6 mg/kg, implicating pathways such as amino acid biosynthesis, protein digestion and absorption, ATP-binding cassette transporters, and aminoacyl-tRNA biosynthesis. Proteomic analysis showed that MC-LR affected distinct pathways, particularly those associated with nucleotide binding, calcium ion binding, ATP binding, cytoskeleton, and actin filament binding. Correlations between differentially expressed metabolites and differentially expressed proteins highlighted critical roles of amino acid biosynthesis, thiamine metabolism, glutathione metabolism, and longevity regulating in earthworms' defense against MC-LR toxicity. This study advances the understanding of molecular pathways underlying MC-LR-induced toxicity in soil invertebrates, providing valuable insights into its ecological impact and potential risks.