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

Ecotoxicol Environ Saf. 2022 Aug:241:113726. doi: 10.1016/j.ecoenv.2022.113726. Epub 2022 Jun 9.

Abstract

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.

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

MeSH terms

  • Animals
  • Bacteria / metabolism
  • Brain / metabolism
  • Brain-Gut Axis
  • Cytokines / metabolism
  • Dysbiosis / chemically induced
  • Fecal Microbiota Transplantation
  • Gastrointestinal Microbiome* / physiology
  • Lipopolysaccharides
  • Mice
  • Polychlorinated Biphenyls* / toxicity
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism

Substances

  • Cytokines
  • Lipopolysaccharides
  • Toll-Like Receptor 4
  • Polychlorinated Biphenyls