Long-term exposure to polystyrene microplastics exacerbates seizure symptoms via lipid metabolic disruption and ferroptosis: insights from multi-omics analyses.

As a consequence of global industrial growth, microplastics (plastic fragments < 5 mm) have become ubiquitous environmental contaminants, prompting serious questions about their impact on human health. Beyond the established risks of ingestion, the inhalation of these airborne particles is now a primary focus, especially regarding potential effects on the neurological system. Emerging evidence from laboratory and animal models shows that inhaled microplastics can penetrate the brain. Once there, they can trigger a cascade of harmful effects, including neuroinflammation, oxidative stress, and deficits in learning and memory. Among the general population, children are uniquely vulnerable to microplastic exposure due to their developing physiological systems, which are particularly susceptible to the chemical and physical hazards posed by these particles. Nevertheless, current scientific understanding of the health consequences of microplastic exposure remains limited, with a substantial knowledge gap concerning the long-term effects of respiratory microplastic exposure on pediatric populations, particularly those with pre-existing neurological conditions such as epilepsy. This study investigates the relationship between chronic respiratory exposure to polystyrene microplastics and seizure severity, with the aim of establishing a potential exposure-metabolite-gene regulatory network. We hypothesize that prolonged respiratory mciroplatsic exposure induces systemic oxidative stress and inflammation, which subsequently disrupts lipid metabolism, alters gene expression profiles, triggers ferroptosis, and ultimately exacerbates seizure manifestations.This study highlights three key findings. First, chronic respiratory microplastic exposure induces systemic oxidative stress and inflammation, posing substantial health risks. Second, integrated metabolomics and Mendelian randomization analyses reveal that this exposure disrupts lipid metabolism, with metabolic perturbations strongly associated with ferroptosis activation and increased seizure severity. Third, multi-omics approaches coupled with in vivo validation confirm that microplastics disrupt lipid homeostasis, dysregulate ferroptosis-related gene expression, and exacerbate seizure manifestations. Notably, our data identify melatonin as a promising therapeutic candidate for mitigating these adverse effects. Collectively, these findings substantially advance the understanding of microplastic-induced neurotoxicity and reveal actionable molecular targets for potential therapeutic interventions.