Gut microbiota dysbiosis induced by polychlorinated biphenyl 126 contributes to increased brain proinflammatory cytokines: Landscapes from the gut-brain axis and fecal microbiota transplantation.
Gut microbiota dysbiosis induced by polychlorinated biphenyl 126 contributes to increased brain proinflammatory cytokines: Landscapes from the gut-brain axis and fecal microbiota transplantation.
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DOI：
10.1016/j.ecoenv.2022.113726
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发表时间：
2022-06
影响因子：
6.8
通讯作者：
Tongtong Li;D. Tian;Mengtian Lu;Bijiao Wang;Jun Li;Baohua Xu;Hao Chen;Shijin Wu
中科院分区：
文献类型：
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作者：
Tongtong Li;D. Tian;Mengtian Lu;Bijiao Wang;Jun Li;Baohua Xu;Hao Chen;Shijin Wu
多氯联苯126(PCB126)引起脑部炎症的机制尚未完全阐明。越来越多的证据表明，微生物-肠道-脑轴在中枢神经系统(CNS)功能障碍中具有相关性。因此，我们旨在研究肠道微生物区系在PCB126诱导的小鼠脑内促炎细胞因子增加中的作用。结果表明，接触PCB126明显扰乱了肠道细菌群落，导致革兰氏阴性菌(如拟杆菌和变形杆菌)的聚集，进一步导致革兰氏阴性细菌脂多糖(LPS)水平升高。随后，细菌内毒素激活结肠Toll样受体4(TLR-4)，促进促炎细胞因子的产生，抑制紧密连接(TJ)蛋白的表达。然后，细菌内毒素从肠腔转移到血液循环并到达大脑，触发内毒素/TLR-4介导的脑促炎细胞因子的增加。粪便微生物区系移植(FMT)后的进一步分析表明，PCB126引起的肠道微生物区系紊乱可诱导细菌内毒素升高，并触发TLR-4介导的脑内促炎细胞因子的增加。这项研究强调了PCB126诱导的肠道微生物区系紊乱导致脑部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，并为调节肠道微生物区系作为环境污染引起的中枢神经系统疾病的治疗靶点开辟了可能性。
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.,BacteroidetesandProteobacteria), 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.