Gut Microbiota from Short-Chain Chlorinated Paraffin-Exposed Mice Promotes Astrocyte Activation by Disrupting the Intestinal Tight Junction via Zonulin Upregulation.
Xinyuan ZhaoTao ZhangYudan ZhengZixuan ZhaoWenjie DingZiyang ZhangZeyao ZhangRui WangMan JiaoLei LiuShali YuXiaoke WangRongrong HuangQiyun WuPublished in: Journal of agricultural and food chemistry (2023)
Short-chain chlorinated paraffins (SCCPs) are novel toxicants in food and are reported to possess neurotoxicity. Here, we investigated the mechanism of SCCP-induced astrocyte activation and neuroinflammation. SCCP gavage induced astrocyte activation and neuronal cell death with the changes of gut microbiome and metabolites. Antibiotic cocktail administration to deplete the gut microbiome ameliorated the astrocyte activation and inflammation induced by SCCPs. In fecal microbiota transplantation (FMT) assays, mice that received transplanted gut microbiome from SCCP-treated mice showed increased astrocyte activation and elevated inflammatory response. In addition, SCCP exposure promotes zonulin expression and tight junction injury, and antibiotic cocktail administration inhibited that in the intestinal tract. Increased zonulin and tight junction injury were also observed in SCCPs_FMT mice. The zonulin inhibition protected the tight junction in the intestinal tract from SCCP exposure and suppressed astrocyte activation. In summary, this study proposes a novel possibility for SCCP-induced astrocyte activation and neurotoxicity by the gut microbiome-mediated zonulin expression and tight junction.
Keyphrases
- blood brain barrier
- inflammatory response
- poor prognosis
- cell death
- high fat diet induced
- oxidative stress
- diabetic rats
- long non coding rna
- high throughput
- climate change
- traumatic brain injury
- type diabetes
- single cell
- toll like receptor
- bone marrow
- cell therapy
- drug induced
- ms ms
- mesenchymal stem cells
- mass spectrometry
- cerebral ischemia
- signaling pathway
- brain injury
- wild type