State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, PR China; College of Marine Ecology and Environment, Shanghai Ocean University, Shanghai 201306, PR China.
State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, PR China.
Sci Total Environ. 2023 Dec 20;905:167009. doi: 10.1016/j.scitotenv.2023.167009. Epub 2023 Sep 11.
The environmental presence of polybrominated diphenyl ethers (PBDEs) is ubiquitous due to their wide use as brominated flame retardants in industrial products. As a common congener of PBDEs, decabromodiphenyl ether (BDE-209) can pose a health risk to animals as well as humans. However, to date, few studies have explored BDE-209's toxic effects on the intestinal tract, and its relevant mechanism of toxicity has not been elucidated. In this study, adult male zebrafish were exposed to BDE-209 at 6 μg/L, 60 μg/L and 600 μg/L for 28 days, and intestinal tissue and microbial samples were collected for analysis to reveal the underlying toxic mechanisms. Transcriptome sequencing results demonstrated a dose-dependent pattern of substantial gene differential expression in the group exposed to BDE-209, and the differentially expressed genes were mainly concentrated in pathways related to protein synthesis and processing, redox reaction, and steroid and lipid metabolism. In addition, BDE-209 exposure caused damage to intestinal structure and barrier function, and promoted intestinal oxidative stress, inflammatory response, apoptosis and steroid and lipid metabolism disorders. Mechanistically, BDE-209 induced intestinal inflammation by increasing the levels of TNF-α and IL-1β and activating the NFκB signaling pathway, and might induce apoptosis through the p53-Bax/Bcl2-Caspase3 pathway. BDE-209 also significantly inhibited the gene expression of rate-limiting enzymes such as Sqle and 3βhsd (p < 0.05) to inhibit cholesterol synthesis. In addition, BDE-209 induced lipid metabolism disorders through the mTOR/PPARγ/RXRα pathway. 16S rRNA sequencing results showed that BDE-209 stress reduced the richness and diversity of intestinal microbiota, and reduced the abundance of probiotics (e.g., Bifidobacterium and Faecalibacterium). Overall, the results of this study help to clarify the intestinal response mechanism of BDE-209 exposure, and provide a basis for evaluating the health risks of BDE-209 in animals.
多溴二苯醚（PBDEs）由于其作为工业产品中的溴化阻燃剂的广泛应用而普遍存在于环境中。十溴二苯醚（BDE-209）作为 PBDEs 的常见同系物，可能对动物和人类的健康构成风险。然而，迄今为止，很少有研究探讨 BDE-209 对肠道的毒性作用，其相关毒性机制也尚未阐明。在这项研究中，成年雄性斑马鱼在 6μg/L、60μg/L 和 600μg/L 的 BDE-209 中暴露 28 天，并收集肠道组织和微生物样本进行分析，以揭示潜在的毒性机制。转录组测序结果表明，暴露于 BDE-209 的组中存在大量基因差异表达，呈剂量依赖性模式，差异表达的基因主要集中在与蛋白质合成和加工、氧化还原反应以及类固醇和脂质代谢相关的途径中。此外，BDE-209 暴露会导致肠道结构和屏障功能受损，并促进肠道氧化应激、炎症反应、细胞凋亡和类固醇和脂质代谢紊乱。从机制上讲，BDE-209 通过增加 TNF-α 和 IL-1β 的水平并激活 NFκB 信号通路引起肠道炎症，并可能通过 p53-Bax/Bcl2-Caspase3 途径诱导细胞凋亡。BDE-209 还显著抑制限速酶如 Sqle 和 3βhsd 的基因表达（p<0.05），以抑制胆固醇合成。此外，BDE-209 通过 mTOR/PPARγ/RXRα 途径诱导脂质代谢紊乱。16S rRNA 测序结果表明，BDE-209 胁迫降低了肠道微生物群的丰富度和多样性，并降低了益生菌（如双歧杆菌和粪杆菌）的丰度。总体而言，这项研究的结果有助于阐明 BDE-209 暴露的肠道反应机制，并为评估 BDE-209 在动物中的健康风险提供依据。
