Metabolomic profiling and pathway level multiomics integration identify shared stress associated and drug specific responses in the parasitic nematode Anisakis simplex s.s.

Anthelmintic exposure can perturb multiple cellular processes in parasitic nematodes, but the metabolic response of Anisakis simplex s.s. remains poorly characterized. Here, we generated untargeted metabolomic profiles of L3 larvae exposed for 12 h to albendazole, ivermectin, or pyrantel and integrated these new data at the pathway level with previously reported transcriptomic and treatment-associated single-nucleotide variant (SNV) datasets generated under matched experimental conditions. Fourteen unique LC–MS features were consistently differentially abundant across all three treatments. One shared feature had two alternative Compound Discoverer annotations (5-hydroxylysine and 4-methoxyestrone) and was counted once at the feature level. Shared changes involved membrane lipids, select amino acid related features, folate/one carbon associated metabolites, and ribose 1-phosphate. These patterns were accompanied by treatment specific quantitative differences; under the concentrations and exposure conditions used, albendazole was associated with the broadest metabolomic alteration. Curated, treatment matched pathway level co-mapping identified convergence in amino acid, purine, tryptophan, and arachidonic acid pathways. No direct gene metabolite correlations were calculated, and annotation dependent low confidence connections were excluded from the curated integration. Overall, the data identify a shared metabolic phenotype together with treatment specific molecular perturbations, involving lipid homeostasis, select amino acid and nucleotide pathways, and redox associated processes, rather than a coordinated hierarchical detoxification or resistance program.