Unraveling Persistent Health Impacts in Mice Following Cessation of Microplastic Exposure: Insights beyond the Surface

The ability of organisms to recover from microplastic (MP) exposure is critical for forming global strategies for MP regulation, risk mitigation, and health protection. However, the recovery dynamics following chronic exposure to environmentally relevant concentrations (ERCs) of MPs remains poorly understood. Here, we present a comprehensive investigation into postexposure recovery following long-term ingestion of polystyrene MPs (40-100 μm) in mice. Animals were fed MPs at either an ERC (approximately 512-2060 particles/day) or a high-dose level (ten times ERC) for 21 weeks, followed by a 4 week recovery period without exposure. Despite cessation of exposure, disruptions in lipid metabolism and gut microbiota persisted in dose- and size-dependent manners, with high-dose groups showing markedly limited recovery. Mechanistic in vitro studies using Caco-2 cells further revealed that MPs impair lipid metabolic homeostasis via sustained suppression of the AMP-activated protein kinase (AMPK) signaling pathway. Together, our findings provide crucial in vivo evidence via a mammalian model that chronic exposure to ERCs of MPs can lead to long-lasting metabolic and microbiome disturbances postexposure. These results underscore the urgency of reassessing the long-term health risks of MPs and developing strategies that address both exposure and postexposure recovery.