Gut microbiota–GABA axis dysregulation underlies polystyrene microplastic (PS-MP) neurotoxicity in rainbow trout: a role for oxidative stress and blood–brain barrier disruption

Microplastics (MPs) threaten aquatic ecosystems and pose potential risks to organismal health through bioaccumulation in aquatic species. This study reveals that 14-day exposure to 5 μm polystyrene microplastics (PS-MPs) (500 μg/L) induces neurocognitive impairment in rainbow trout (Oncorhynchus mykiss), a globally consumed aquaculture species. MPs accumulated in brain and gut tissues, causing blood-brain barrier structural alterations, intestinal mucosal damage, and oxidative stress. Multi-omics analysis revealed associations between gut microbiota dysbiosis (reduced Ralstonia, increased Acinetobacter) to suppressed neuroactive pathways, particularly GABA synthesis and transport. Downregulation of monocarboxylate transporters (mct1/2) and GABA-related enzymes (GAD1/2) disrupted gut-to-brain GABA homeostasis, neurobehavioral deficits. These findings establish the gut microbiota-GABA axis as a critical mediator of MPs neurotoxicity, highlighting risks to seafood safety and necessitating urgent regulation of microplastic contamination in aquatic food chains.