Gut microbiota dysbiosis induced by polychlorinated biphenyl 126 contributes to increased brain proinflammatory cytokines: Landscapes from the gut-brain axis and fecal microbiota transplantation

Ecotoxicology and Environmental Safety

Dongcan Tian¹  Shijin Wu¹  Bijiao Wang¹  Baohua Xu¹  Mengtian Lu¹  Tongtong Li¹  Hao Chen¹  Jun Li² 

[1] 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;

关键词: Polychlorinated biphenyl 126;    Brain proinflammatory cytokines;    Gut bacterial community;    Toll-like receptor 4;    Fecal microbiota transplantation;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown