Department of Applied Biology, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.
Jiangxi Key Laboratory of Natural Product and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang 330045, China.
Ecotoxicol Environ Saf. 2022 Aug;241:113726. doi: 10.1016/j.ecoenv.2022.113726. Epub 2022 Jun 9.
The pathogenesis of brain inflammation induced by polychlorinated biphenyl 126 (PCB126) has not yet been fully illustrated. Growing evidence highlights the relevance of the microbiota-gut-brain axis in central nervous system (CNS) dysfunction. Therefore, we aimed to study the role of the gut microbiota in PCB126-induced proinflammatory cytokine increases in the mouse brain. The results showed that PCB126 exposure significantly disordered gut bacterial communities, resulting in the enrichment of gram-negative bacteria (e.g., Bacteroidetes and Proteobacteria), further leading to elevated levels of the gram-negative bacterial lipopolysaccharide (LPS). Subsequently, colonic toll-like receptor 4 (TLR-4) was activated by bacterial LPS, which promoted proinflammatory cytokine generation and inhibited tight junction (TJ) protein expression. Then, bacterial LPS translocated from the gut lumen into the blood circulation and reached the brain, triggering LPS/TLR-4-mediated increases in brain proinflammatory cytokines. Further analysis after fecal microbiota transplantation (FMT) suggested that the gut microbiota disturbance caused by PCB126 could induce elevated bacterial LPS and trigger TLR-4-mediated increases in proinflammatory cytokines in the brain. This study highlights the possibility that PCB126-induced gut microbiota disorder contributes to increased brain proinflammatory cytokines. These results provide a new perspective for identifying the toxicity mechanisms of PCB126 and open up the possibility of modulating the gut microbiota as a therapeutic target for CNS disease caused by environmental pollution.
多氯联苯 126（PCB126）引起的脑炎症发病机制尚未完全阐明。越来越多的证据强调了微生物群-肠-脑轴在中枢神经系统（CNS）功能障碍中的相关性。因此，我们旨在研究肠道微生物群在 PCB126 诱导的小鼠大脑促炎细胞因子增加中的作用。结果表明，PCB126 暴露显著扰乱了肠道细菌群落，导致革兰氏阴性菌（如拟杆菌门和变形菌门）富集，进而导致革兰氏阴性菌脂多糖（LPS）水平升高。随后，细菌 LPS 激活结肠 Toll 样受体 4（TLR-4），促进促炎细胞因子的产生并抑制紧密连接（TJ）蛋白的表达。然后，细菌 LPS 从肠腔易位到血液循环并到达大脑，引发 LPS/TLR-4 介导的大脑促炎细胞因子增加。粪便微生物群移植（FMT）后的进一步分析表明，PCB126 引起的肠道微生物群紊乱可导致细菌 LPS 升高，并触发 TLR-4 介导的大脑促炎细胞因子增加。这项研究强调了 PCB126 诱导的肠道微生物群紊乱可能导致大脑促炎细胞因子增加的可能性。这些结果为确定 PCB126 的毒性机制提供了新的视角，并为作为环境污染引起的 CNS 疾病的治疗靶点调节肠道微生物群开辟了可能性。
