Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019, China.
Department of Pathology, Affiliated Hospital of Nantong University, Nantong 226001, China.
J Agric Food Chem. 2023 May 31;71(21):8192-8202. doi: 10.1021/acs.jafc.3c01058. Epub 2023 May 19.
Short-chain chlorinated paraffins (SCCPs) are novel toxicants in food and are reported to possess neurotoxicity. Here, we investigated the mechanism of SCCP-induced astrocyte activation and neuroinflammation. SCCP gavage induced astrocyte activation and neuronal cell death with the changes of gut microbiome and metabolites. Antibiotic cocktail administration to deplete the gut microbiome ameliorated the astrocyte activation and inflammation induced by SCCPs. In fecal microbiota transplantation (FMT) assays, mice that received transplanted gut microbiome from SCCP-treated mice showed increased astrocyte activation and elevated inflammatory response. In addition, SCCP exposure promotes zonulin expression and tight junction injury, and antibiotic cocktail administration inhibited that in the intestinal tract. Increased zonulin and tight junction injury were also observed in SCCPs_FMT mice. The zonulin inhibition protected the tight junction in the intestinal tract from SCCP exposure and suppressed astrocyte activation. In summary, this study proposes a novel possibility for SCCP-induced astrocyte activation and neurotoxicity by the gut microbiome-mediated zonulin expression and tight junction.
短链氯化石蜡（SCCPs）是食品中的新型有毒物质，据报道具有神经毒性。在这里，我们研究了 SCCP 诱导的星形胶质细胞激活和神经炎症的机制。SCCP 灌胃诱导星形胶质细胞激活和神经元细胞死亡，同时改变了肠道微生物组和代谢物。抗生素鸡尾酒给药以耗尽肠道微生物组可改善 SCCP 引起的星形胶质细胞激活和炎症。在粪便微生物群移植（FMT）实验中，接受来自 SCCP 处理小鼠的移植肠道微生物组的小鼠表现出星形胶质细胞激活增加和炎症反应升高。此外，SCCP 暴露促进了 zonulin 的表达和紧密连接损伤，而抗生素鸡尾酒给药抑制了肠道中的 zonulin 表达和紧密连接损伤。在 SCCPs_FMT 小鼠中也观察到 zonulin 表达和紧密连接损伤增加。zonulin 抑制可保护肠道中由 SCCP 暴露引起的紧密连接并抑制星形胶质细胞激活。总之，这项研究提出了一种新的可能性，即通过肠道微生物组介导的 zonulin 表达和紧密连接，SCCP 诱导星形胶质细胞激活和神经毒性。
