Unraveling olanzapine toxicity in planarian: Multi-omics reveals mechanisms of behavioral and regenerative deficits.

The pervasive release of antipsychotic pharmaceuticals into aquatic environments poses significant ecotoxicological risks. An integrated multi-omics framework was employed to comprehensively elucidate the toxicological effects and underlying mechanisms of olanzapine (OLA) on the freshwater planarian Dugesia constrictiva. Exposure to environmentally relevant (0.5 μg L-1) and elevated (5 μg L-1) concentrations of OLA induced significant morphological alterations and behavioral deficits. Pronounced neurotoxicity was evidenced by severe damage to the central nervous system, culminating in the complete loss of neural structures at higher concentrations. OLA exposure significantly impaired planarian regeneration, accompanied by alterations in stem cell proliferation and differentiation. Transcriptomic analysis revealed that OLA exposure dysregulated key cellular pathways, enhancing autophagy while suppressing neurodevelopment, immune function, and apoptosis. Metabolomic profiling further confirmed profound disruptions in energy metabolism and biosynthetic pathways, including the downregulation of steroid hormone biosynthesis and diverse amino acid metabolism. Moreover, OLA exposure induced significant shifts in the planarian microbiome, characterized by reduced alpha diversity, the emergence of opportunistic pathogens (Legionella), and a marked depletion of dominant taxa (Rhodoferax), indicating OLA-induced microbial dysbiosis. Collectively, our results provide novel mechanistic insights into the complex, cascading ecotoxicological effects of OLA on a representative aquatic invertebrate and underscore the significant environmental hazards posed by pharmaceutical contaminants in aquatic ecosystems.