The Role Of Sustained Endoplasmic Reticulum Stress Induced By Gut Microbiome In Intestinal Fibrosis Of Inflammatory Bowel Disease

IBD is a group of chronic illness in intestinal charactiried of intestinall inflammation. CD and UC are the two main types of IBD in clinic. With the development of the intestinal inflammation, the injury of the intestine is more and more harmful. And the remodling of the intestine is also caused, eventually, the inflammation developes into intestinal fibriosis. In this phase, not only the basic function of the intesetine is lost, but also more and more complications appear. The stenosis caused by intestinal fibrosis is the mainly reason of the irreversible factor in IBD, which caused the surgery. There are some evidences that proved the sustained endoplasmic reticulum stress (ERS) is associated with fibrosis, making it a possible mechanism for fibrosis. Therefore, we designed three parts of experiments to investigate the role of sustained endoplasmic reticulum stress induced by gut microbiome in intestinal fibrosis of inflammatory bowel disease.Part 1 the expression of ERS in the nostenosis sites of UC patientsObjective:we design this clinic and experiment to explore the role of the sustained endoplasmic reticulum stress in the intestinal fibrosis of inflammatory bowel disease.Methods:In the first part, we mainly studied in clinical ulcerative colitis patients, which are in the remission phase. We picked the stenosis sites and the nostenosis sites from the UC patients, camparing them with the normal colon sites of the patiens with colon cancer. By detecting the extracelluar depositon and fibrosis degree and the expression of the ERS related proteins, we studied the expression of ERS in the stenosis sites of UC patients.Results:In the first part, we successed in proving that, the fibrosis degree and expression of the ERS proteins, in the stenosis sites of UC patients’colon speciments, are significantly increased, comparing with the nostenosis sites of UC patients and the normal colon from the patients with colon cance.Conclusions:The expression of intestinal fibrosis is high in the stenosis sites of UC patients’colon speciments. And the sustained endoplasmic reticulum stress induced is one of the mechanism of intestinal fibrosis in UC.Part 2 the role of ERS in the intestinal fibrosis models caused by TNBSObjective:We designed this mouse experiment to to explore the role of the sustained endoplasmic reticulum stress in the intestinal fibrosis of inflammatory bowel disease.Methods:In the second part of the experiment, we used TNBS to induce the IBD intestinal fibrosis models in mouses. And to explore the role of the ERS in the intestinal fibrosis of IBD, we obsevered the fibrosis degree and the expression of the ERS proteins after adding the TUDCA, which is the protector of the ERS.Results:In the first part, we found that, in intestinal fibrosis models of IBD caused by TNBS, the ERS proteins are significantly increased, and that restraining ERS can weaken intestinal fibrosis.Conclusions:In the intestinal fibrosis models caused by TNBS, TUDCA can decresed the expression of intestinal fibrosis caused by TNBS. And the sustained endoplasmic reticulum stress induced is one of the mechanism of intestinal fibrosis caused by TNBS.Part 3 the role of improving the intestinal flora in the expression of ERS in intestinal fibrosis models caused by TNBSObjective:We designed this mouse experiment to to explore the role of the sustained endoplasmic reticulum stress in the intestinal fibrosis of inflammatory bowel disease.Methods:In this third part of the experiments, based on the intestinal fibrosis models of IBD induced by TNBS, we added the pectin and sodium butyrate to modify the gut microbiota. Then we observed the fibrosis degree and the expression of ERS proteins, and analysised the changes of the intestinal flora with the intestinal fllra analysis.Results:In the first part, we use to pectin and sodium butyrate to improve the intestinal flora. We found that, in intestinal fibrosis models of IBD caused by TNBS, improving the intestinal flora can reduce ERS and the intestinal fibrosis.Conclusions:The sustained endoplasmic reticulum stress induced by gut microbiome is one of the mechanism of intestinal fibrosis in inflammatory bowel disease. And improving the intestinal flora can effectively reduces the sustained ERS, causing the remission of intestinal fibrosis.