Qiu Haixia, Gao Hui, Yu Fangjin, Xiao Boya, Li Xiaoning, Cai Bo, Ge Long, Lu Yinting, Wan Zhengyi, Wang Yafei, Xia Tao, Wang Aiguo, Zhang Shun
Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; MOE Key Laboratory of Environment and Health, State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Clinical Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Sci Total Environ. 2022 Jun 15;825:154150. doi: 10.1016/j.scitotenv.2022.154150. Epub 2022 Feb 24.
Polybrominated diphenyl ethers (PBDEs), a major class of flame retardants, have been extensively applied in plastics, electrical equipment, textile fabrics, and so on. Early-life exposure to PBDEs is correlated to neurobehavioral deficits in adulthood, yet the underlying mechanism has not been fully understood. Increasing evidence has demonstrated that gut microbiota dysbiosis and serum metabolites alterations play a role in behavioral abnormalities. However, whether their perturbation is implicated in PBDEs-induced neurotoxicity remains unclear. Here, we sought to explore the effects of developmental exposure to environmentally relevant levels of 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47), a major congener in human samples, on gut microbiota and serum metabolic profile as well as their link to neurobehavioral parameters in adult rats. The open field test showed that gestational and lactational exposure to PBDE-47 caused hyperactivity and anxiety-like behavior. Moreover, 16S rRNA sequencing of fecal samples identified a distinct community composition in gut microbiota following PBDE-47 exposure, manifested as decreased genera Ruminococcaceae and Moraxella, increased families Streptococcaceae and Deferribacteraceae as well as genera Escherichia-Shigella, Pseudomonas and Peptococcus. Additionally, the metabolomics of the blood samples based on liquid chromatography-mass spectrometry revealed a significant shift after PBDE-47 treatment. Notably, these differential serum metabolites were mainly involved in amino acid, carbohydrate, nucleotide, xenobiotics, and lipid metabolisms, which were further validated by pathway analysis. Importantly, the disturbed gut microbiota and the altered serum metabolites were associated with each other and with neurobehavioral disorders, respectively. Collectively, these results suggest that gut microbiota dysbiosis and serum metabolites alterations potentially mediated early-life low-dose PBDE-47 exposure-induced neurobehavioral impairments, which provides a novel perspective on understanding the mechanisms of PBDE-47 neurotoxicity.
多溴二苯醚（PBDEs）是一类主要的阻燃剂，已广泛应用于塑料、电气设备、织物等领域。生命早期接触PBDEs与成年期的神经行为缺陷相关，但其潜在机制尚未完全明确。越来越多的证据表明，肠道微生物群失调和血清代谢物改变在行为异常中起作用。然而，它们的扰动是否与PBDEs诱导的神经毒性有关仍不清楚。在此，我们试图探究发育阶段暴露于环境相关水平的2,2',4,4'-四溴二苯醚（PBDE-47，人类样本中的主要同系物）对成年大鼠肠道微生物群和血清代谢谱的影响，以及它们与神经行为参数的关联。旷场试验表明，孕期和哺乳期暴露于PBDE-47会导致多动和焦虑样行为。此外，粪便样本的16S rRNA测序确定了PBDE-47暴露后肠道微生物群中独特的群落组成，表现为瘤胃球菌科和莫拉克斯氏菌属减少，链球菌科和脱铁杆菌科以及大肠杆菌-志贺氏菌属、假单胞菌属和消化球菌属增加。此外，基于液相色谱-质谱联用的血液样本代谢组学分析显示，PBDE-47处理后有显著变化。值得注意的是，这些差异血清代谢物主要参与氨基酸、碳水化合物、核苷酸、外源性物质和脂质代谢，通过通路分析进一步得到验证。重要的是，肠道微生物群紊乱和血清代谢物改变分别相互关联且与神经行为障碍相关。总体而言，这些结果表明，肠道微生物群失调和血清代谢物改变可能介导了生命早期低剂量PBDE-47暴露诱导的神经行为损伤，这为理解PBDE-47神经毒性机制提供了新的视角。
