Microplastic-induced gut dysbiosis and metabolic alterations in juvenile European seabass (Dicentrarchus labrax): A multi-omics approach

: Environmental microplastics (MPs) are increasingly recognized as emerging contaminants with the potential to disrupt intestinal homeostasis in marine organisms. However, most experimental evidence is based on pristine particles rather than environmentally weathered forms. This study investigated the intestinal effects of environmentally derived microplastics (EMPs) in juvenile European seabass (Dicentrarchus labrax) using an integrated multi-omics approach. Fish were exposed for five days to two concentrations of EMPs (0.5 and 1 mg/kg of feed), followed by analyses combining histological, transcriptomic, metabolomic, and metagenomic endpoints. EMP exposure led to significant particle accumulation in gut tissues, predominantly consisting of small polyethylene fragments. Gene expression and immunofluorescence analyses revealed activation of p53 and Caspase-3 mediated apoptosis together with NF-κB and IL-6 driven inflammatory signalling, indicating concurrent oxidative and immune stress. Untargeted metabolomics identified marked alterations in lipid metabolism, redox regulation, and amino acid turnover, consistent with mitochondrial dysfunction and impaired energy homeostasis. Parallel metagenomic profiling revealed subtle but coherent shifts in gut bacterial communities, with enrichment of pollutant-tolerant taxa such as Acidovorax and Halioglobus and reduction of beneficial commensals such as Ligilactobacillus. Multi-omics data integration demonstrated a coordinated restructuring of microbial and metabolic networks underlying host physiological stress. Collectively, these findings highlight the intestine as a primary target of microplastic toxicity and provide mechanistic insight into early biological responses to environmentally realistic microplastic exposure in marine fish.