National Medical Products Administration (NMPA) Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China.
Department of Cardiovascular Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
ACS Nano. 2024 Sep 3;18(35):24044-24059. doi: 10.1021/acsnano.4c03874. Epub 2024 Aug 19.
Oral ingestion is the primary route for human exposure to nanoplastics, making the gastrointestinal tract one of the first and most impacted organs. Given the presence of the gut-brain axis, a crucial concern arises regarding the potential impact of intestinal damage on the neurotoxic effects of nanoplastics (NPs). The intricate mechanisms underlying NP-induced neurotoxicity through the microbiome-gut-brain axis necessitate further investigation. To address this, we used mice specifically engineered with nuclear factor erythroid-derived 2-related factor 2 () deficiency in their intestines, a strain whose intestines are particularly susceptible to polystyrene NPs (PS-NPs). We conducted a 28-day repeated-dose oral toxicity study with 2.5 and 250 mg/kg of 50 nm PS-NPs in these mice. Our study delineated how PS-NP exposure caused gut microbiota dysbiosis, characterized by and proliferation, resulting in increased levels of interleukin 17C (IL-17C) production in the intestines. The surplus IL-17C permeated the brain via the bloodstream, triggering inflammation and brain damage. Our investigation elucidated a direct correlation between intestinal health and neurological outcomes in the context of PS-NP exposure. Susceptible mice with fragile guts exhibited heightened neurotoxicity induced by PS-NPs. This phenomenon was attributed to the elevated abundance of microbiota associated with IL-17C production in the intestines of these mice, such as and , provoked by PS-NPs. Neurotoxicity was alleviated by treatment with anti-IL-17C-neutralizing antibodies or antibiotics. These findings advanced our comprehension of the regulatory mechanisms governing the gut-brain axis in PS-NP-induced neurotoxicity and underscored the critical importance of maintaining intestinal health to mitigate the neurotoxic effects of PS-NPs.
经口摄入是人类接触纳米塑料的主要途径，这使得胃肠道成为纳米塑料（NPs）最先接触和受影响最大的器官之一。鉴于肠道-大脑轴的存在，人们对肠道损伤对纳米塑料神经毒性的潜在影响产生了极大的关注。通过微生物群-肠道-大脑轴，纳米塑料引起神经毒性的复杂机制需要进一步研究。为了解决这个问题，我们使用了在肠道中缺乏核因子红细胞衍生 2 相关因子 2 () 的特定基因工程小鼠，这种小鼠的肠道对聚苯乙烯 NPs（PS-NPs）特别敏感。我们对这些小鼠进行了为期 28 天的重复口服毒性研究，使用 50nm PS-NPs 的 2.5 和 250mg/kg 剂量。我们的研究描绘了 PS-NP 暴露如何导致肠道微生物群失调，表现为 和 增殖，导致肠道中白细胞介素 17C (IL-17C) 的产生水平增加。过剩的 IL-17C 通过血液渗透到大脑，引发炎症和大脑损伤。我们的研究阐明了 PS-NP 暴露情况下肠道健康与神经学结果之间的直接相关性。肠道脆弱的易感小鼠表现出由 PS-NPs 引起的更高神经毒性。这种现象归因于与肠道中 IL-17C 产生相关的微生物群丰度的增加，例如在这些小鼠的肠道中，PS-NPs 会引起 和 等微生物群的增加。用抗 IL-17C 中和抗体或抗生素进行治疗可以减轻神经毒性。这些发现促进了我们对肠道-大脑轴在 PS-NP 诱导的神经毒性中调控机制的理解，并强调了维持肠道健康以减轻 PS-NPs 神经毒性的重要性。
