Wang Chenfei, Deng Hongyu, Wang Dongbin, Wang Jiating, Huang Hairong, Qiu Jiayi, Li Yinfei, Zou Tangbin, Guo Lianxian
Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, China; Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen 518000, China.
Shenzhen Academy of Metrology and Quality Inspection, Shenzhen 518110, China.
Ecotoxicol Environ Saf. 2021 Nov 18;228:112935. doi: 10.1016/j.ecoenv.2021.112935.
Arsenic can cause neurodegenerative diseases of the brain, but the definite mechanism is still unknown. In this study, to discuss the disturbances on brain metabolome and lipidome under subchronic arsenic exposure, we treated mice with the arsenic-containing feed (concentration of total arsenic = 30 mg/kg) prepared in accordance with the proportion of rice arsenicals for 16 weeks and performed metabolomics and lipidomics studies respectively using UHPLC-Triple-TOF-MS/MS and UHPLC-Q Exactive Focus MS/MS on mice brain. In addition, the distributions of arsenical metabolites along the feed-gut-blood-brain chain were analyzed by ICP-MS and HPLC-ICP-MS, and fecal microbial variations were investigated by 16 s sequencing. The data showed that although only a tiny amount of arsenic (DMA=0.101 mg/kg, uAs=0.071 mg/kg) enters the brain through the blood-brain barrier, there were significant changes in brain metabolism, including 118 metabolites and 17 lipids. These different metabolites were involved in 30 distinct pathways, including glycometabolism, and metabolisms of lipid, nucleic acid, and amino acid were previously reported to be correlated with neurodegenerative diseases. Additionally, these different metabolites were significantly correlated with 12 gut bacterial OTUs, among which Lachnospiraceae, Muribaculaceae, Ruminococcaceae, and Erysipelotrichaceae were also previously reported to be related to the distortion of metabolism, indicating that the disturbance of metabolism in the brain may be associated with the disturbance of gut microbes induced by arsenic. Thus, the current study demonstrated that the brain metabolome and lipidome were significantly disturbed under subchronic arsenic exposure, and the disturbances also significantly correlated with some gut microbiome and may be associated with neurodegenerative diseases. Although preliminary, the results shed some light on the pathophysiology of arsenic-caused neurodegenerative diseases.
砷可引发脑部神经退行性疾病，但其确切机制仍不明晰。在本研究中，为探讨亚慢性砷暴露对脑代谢组和脂质组的干扰，我们用按照大米砷含量比例配制的含砷饲料（总砷浓度 = 30毫克/千克）对小鼠进行处理16周，并分别使用超高效液相色谱-三重四极杆飞行时间质谱联用仪（UHPLC-Triple-TOF-MS/MS）和超高效液相色谱-高分辨质谱仪（UHPLC-Q Exactive Focus MS/MS）对小鼠脑进行代谢组学和脂质组学研究。此外，通过电感耦合等离子体质谱仪（ICP-MS）和高效液相色谱-电感耦合等离子体质谱联用仪（HPLC-ICP-MS）分析砷代谢产物沿饲料-肠道-血液-脑链的分布情况，并通过16s测序研究粪便微生物变化。数据显示，尽管仅有极少量的砷（二甲基砷 = 0.101毫克/千克，无机砷 = 0.071毫克/千克）通过血脑屏障进入大脑，但脑代谢仍发生了显著变化，包括118种代谢产物和17种脂质。这些不同的代谢产物涉及30条不同的通路，包括糖代谢，且先前报道脂质、核酸和氨基酸代谢与神经退行性疾病相关。此外，这些不同的代谢产物与12种肠道细菌操作分类单元显著相关，其中毛螺菌科、Muribaculaceae、瘤胃球菌科和丹毒丝菌科先前也被报道与代谢紊乱有关，这表明脑中代谢紊乱可能与砷诱导的肠道微生物紊乱有关。因此，本研究表明亚慢性砷暴露下脑代谢组和脂质组受到显著干扰，且这些干扰也与一些肠道微生物群显著相关，可能与神经退行性疾病有关。尽管结果尚属初步，但为砷致神经退行性疾病的病理生理学研究提供了一些线索。
