Integrated Metabolomic and Proteomic Analyses Reveal Altered Iron Homeostasis and Immunometabolic Remodeling in the Spleen of Solea senegalensis during Vibriosis

Vibrio anguillarum is a major pathogen impacting Solea senegalensis aquaculture. While host–pathogen competition for iron drives disease progression, the in vivo molecular evidence linking iron homeostasis and immune responses in fish remains limited. Here, we integrated metabolomic and proteomic analyses to characterize the splenic response of S. senegalensis during experimental vibriosis. Multiomics integration revealed disruption of iron homeostasis alongside coordinated immunometabolic reprogramming. We detected the bacterial siderophore piscibactin directly in spleen tissue of sole exhibiting advanced stages of vibriosis, providing in vivo evidence of siderophore-mediated iron acquisition. Infection-driven metabolic shifts in lysine degradation, nucleotide metabolism, and mitochondrial energy pathways were correlated with heightened cellular proliferation and metabolic stress. Integrative analysis identified metabolites including 2-aminoadipic acid, saccharopine, and methylsuccinic acid, together with iron-regulatory proteins (e.g., STEAP4) as candidate biomarkers. These findings enhance our understanding of vibriosis-associated immunometabolic responses and provide a systems-level framework for future disease monitoring and management in aquaculture.