Correlation Study Between The Changes Of Intestinal Microflora And Oxidative Damage Of Small Intestine Under Tetrabromobisphenol A Stress In Rats

Tetrabromobisphenol A(TBBPA)is one of the most widely used bromine flame retardants,which constantly leaks to various environmental medias and biological organisms.TBBPA have attracted immense attention due to its potential threat to humans and environment worldwide.The toxic effects of TBBPA on biological organism mainly focus on liver toxicity,neurotoxicity,reproductive toxicity and so on.Gut microbiota are critically relevant to host health.However,its toxicological understanding reports on gut microbiota and intestinal health are numbered.In this study,we selected male Sprague-Dawley rats,which were divided into control group(0 mg/kg WB),low-dose group(10 mg/kg WB),medium-dose group(100 mg/kg WB),high-dose group(1000 mg/kg WB),recovery control group(0 mg/kg WB)and recovery group(1000 mg/kg WB).TBBPA was continuously exposed to the rats for 6 weeks by oral gavage.After exposure,the recovery control group(0 mg/kg WB)and the recovery group(1000 mg/kg WB)recovered naturally for one week.We tried to investigate the correlation between intestinal microflora structure changes and oxidative damage of small intestine in SD rats under TBBPA stress.The results of oxidative damage in the rats' small intestine showed that: After exposure to 1000 mg/kg TBBPA,the growth and development of rats were affected,resulting in a significant decrease in body weight and daily food intake;TBBPA induced the necrosis of epithelial mucosal cells,mitochondrial swelling and interstitial hyperemia in the tissue of duodenum,jejunum and ileum.After a week of natural recovery,the morphological damage was relieved;we found that TBBPA caused the height of the villi to become shorter,the depth of the crypt to become longer,and the ratio of the villi's height to the crypt's depth to decrease in the tissue of duodenum,jejunum and ileum,which affected absorption and digestion;The ROS level increased significantly,and the activity of related antioxidant enzymes(CAT,T-SOD and GSH-PX)decreased significantly.TBBPA destroyed the balance of oxidation and antioxidation in tissue;TBBPA activated the rat duodenal,jejunal and ileal oxidative stress signaling pathway Keap1-Nrf2-ARE,resulting Keap1,Nrf2,HO-1,GCLC,GST and NQO1 genes which were related to the regulation of oxidative stress upregulation,while cell permeability related gene TJP2 downregulated.After a week of natural recovery,compared with the high-dose group,the expression level of Keap1,Nrf2,HO-1,GCLC,GST and NQO1 genes was significantly reduced,while the expression level of TJP2 was significantly increased in the recovery group.The results of intestinal microflora in rats showed that: The intestinal microbial abundance and diversity of rats were significantly decreased in rats exposed to 100-1000 mg/kg TBBPA,resulting the decreasing of Chao index and Shannon index;Exposed to 1000 mg/kg TBBPA,the relative abundance of Bacteroidetes and Firmicutes in the rats' gut microbes decreased significantly,while the relative abundance of Proteobacteria,Fusobacteria and Verrucomicrobia increased significantly,resulting in changes in the composition of intestinal microorganisms.Karl-Pearson correlation analysis showed that: The relative abundance of Firmicutes and the ratio of Firmicutes/Bacteroidetes were positively correlated with the body weight of rats,and these two microorganisms might be involved in regulating the growth and development of rats;The relative abundance of Akkermansia was positively correlated with GSH content while negatively correlated with GSH-PX activity,and this suggested that Akkermansia may inhibit the activity of GSH0PX;Bacteroides and Bacteroidales S24-7 group_norank were the key bacterias in the process of injury,which had a large number of genes encoding enzymes,and they might be involved in the metabolism of TBBPA.Above all,TBBPA caused oxidative damage to the duodenum,jejunum and ileum of rats,activating the oxidative stress signaling pathway Keap1-Nrf2-ARE,and changed the composition and structure of intestinal microorganisms.In addition,Bacteroides and Bacteroidales S24-7 group_norank were closely related to the oxidative damage process.The above research provided theoretical basis for risk assessment under TBBPA exposure.