Yang Ge, Li Min, Zheng Xinyue, Chen Xinyue, Peng Yang, Li Jinghan, Yang Shuiqing, Chen Hao, Wang Yifei, Zhang Haiying, Gong Cunyi, Hu Fei, Wan Jian, Zhu Zhihong, Zhang Ling, Li Rui
Key Laboratory of Pesticide & Chemical Biology of the Ministry of Education, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China.
Institute of Nanoscience and Nanotechnology, College of Physical Science and Technology, Central China Normal University, Wuhan 430079, China.
ACS Nano. 2025 May 27;19(20):19233-19254. doi: 10.1021/acsnano.5c01639. Epub 2025 May 13.
As an emerging contaminant, nanoplastics have evolved into a global ecological issue. Studies have shown that nanoplastics induce neurotoxicity across species, however, the causal mechanism remains unknown. This study aimed to explore the mechanism underlying the neurotoxicity caused by polystyrene nanoplastics (PS-NPs) via microbiota-gut-brain axis in immature mice, which serve as a model of infants and young children who are at higher exposure risk to NPs. The results indicated that while only a minority of PS-NPs reached the brain after exposure, they still had significant neurotoxic effects, as reflected by abnormalities in behavior, biochemical marker levels and histopathology. Proteomics and quantification analyses revealed that a proteostasis imbalance mediated by lysosomal and proteasome dysfunction in the brain is the key reason for the induced neurotoxicity. Further, we confirmed the indirect role of gut microbiota in the neurotoxicity induced by PS-NPs through 16S rDNA analyses and fecal microbiota transplantation. Crucial bacterial species such as potentially act as indicators for gut dysbiosis after PS-NPs exposure. Notably, we first estimated the indirect effect of gut microbiota on neurotoxicity attributed to PS-NPs in immature mice as 39.20% by high-dimensional mediation analysis. Trehalose was identified as a mediator connecting the gut microbiota and the brain, and the crucial role of trehalose supplementation was highlighted in remodeling the brain proteostasis to alleviate the neurotoxicity in immature mice. These findings are expected to contribute to a deeper understanding of the risk assessment and health protection of the nervous system from exposure to PS-NPs early in life.
作为一种新兴污染物，纳米塑料已演变成一个全球性的生态问题。研究表明，纳米塑料会在不同物种间诱发神经毒性，然而，其因果机制仍不明晰。本研究旨在探讨聚苯乙烯纳米塑料（PS-NPs）通过微生物群-肠道-脑轴在幼鼠中引发神经毒性的潜在机制，幼鼠可作为对纳米塑料暴露风险较高的婴幼儿的模型。结果表明，虽然暴露后仅有少数PS-NPs进入大脑，但它们仍具有显著的神经毒性作用，这可从行为、生化标志物水平及组织病理学异常中得到反映。蛋白质组学和定量分析显示，大脑中由溶酶体和蛋白酶体功能障碍介导的蛋白质稳态失衡是诱发神经毒性的关键原因。此外，我们通过16S rDNA分析和粪便微生物群移植证实了肠道微生物群在PS-NPs诱导的神经毒性中的间接作用。关键细菌物种如 在PS-NPs暴露后可能作为肠道菌群失调的指标。值得注意的是，我们首次通过高维中介分析估计，在幼鼠中肠道微生物群对PS-NPs所致神经毒性的间接影响为39.20%。海藻糖被确定为连接肠道微生物群和大脑的介质，补充海藻糖在重塑大脑蛋白质稳态以减轻幼鼠神经毒性方面的关键作用也得到了凸显。这些发现有望有助于更深入地理解生命早期暴露于PS-NPs对神经系统的风险评估和健康保护。
