Fragile Guts Make Fragile Brains: Intestinal Epithelial Nrf2 Deficiency Exacerbates Neurotoxicity Induced by Polystyrene Nanoplastics

作者：Boxuan Liang, Yanhong Deng, Yuji Huang, Yizhou Zhong, Zhiming Li, Jiaxin Du, Rongyi Ye, Yujie Feng, Ruobing Bai, Bingchi Fan, Xiaoqing Chen, Xiyun Huang, Xiaohong Yang, Hongyi Xian, Xingfen Yang, Zhenlie Huang · 发表于：ACS Nano · 年份：2024 · DOI：10.1021/acsnano.4c03874 · 被引用次数：41 · 研究领域：Microplastics and Plastic Pollution、Graphene and Nanomaterials Applications、biodegradable polymer synthesis and properties

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 ( Nrf2 ) 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 Mycoplasma and Coriobacteriaceae 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 Meso...