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Characteristics Of Gut Microbiota In Patients With Inflammatory Bowel Disease And Fecal Microbiota Transplantation For Ulcerative Colitis

Posted on:2020-06-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y Y FanFull Text:PDF
GTID:1524306632950949Subject:Physiology
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Inflammatory bowel disease is a chronic intestinal inflammatory disease,and its incidence has increased year by year,which has become a worldwide problem.The pathogenesis of this disease is not clear,and there are still quite a few patients with conventional treatments that have poor efficacy.In recent years,it has been found that intestinal flora imbalance plays an important role in the development of inflammatory bowel disease,and the intestinal flora may have characteristic changes in inflammatory bowel disease.Regulation of intestinal microecology may be a new therapy for inflammatory bowel disease.Among them,fecal bacteria transplantation as an important means to reconstruct the intestinal micro-ecological balance is considered to have therapeutic value for inflammatory bowel disease.Therefore,exploring the changes of intestinal flora in inflammatory bowel disease,elaborating the correlation between intestinal flora and the pathogenesis of inflammatory bowel disease,establishingthe diagnostic model of intestinal flora,and exploring the therapeutic effect of fecal bacteria transplantation on inflammatory bowel disease are of great significance for the diagnosis and treatment of inflammatory bowel disease.In this study high-throughput sequencing technology of 16S rDNA combining R analysis has been used to explore the intestinal flora structure in patients with Crohn’s disease and ulcerative colitis.The results showed an obvious change of intestinal microbial community.Decreased of richness and diversity has happened in bacteriain patient with Crohn’s disease and ulcerative colitis.Also,some differential flora has been found in different level of classification.Further analysis found that patients with Crohn’s disease and ulcerative colitis have higher abundance of pathogenic bacteria(such as Escherichia-Shigella,Vesococcus,etc.),and lower abundance of bacteria that have anti-inflammatory effects(such as Bacteroides,Koalabacterium,Rossella,etc).In additon,the ROC curve analysis shows a pretty good accuracy of these flora to identify the patiens,which is up to above 0.85.Furthermore,through COG and KEGG analysis,it is found that unlike CD,the difference in functional annotation of UC is mainly related to the recognition and transformation of bacteria,suggesting that the intestinal flora may be more closely related to the occurrence and development of UC.To explore the therapeutic effect of fecal bacteria transplantation on ulcerative colitis,patients with ulcerative colitis who had poor treated by coutine therapy were taken as the research objects,enteric-capsules were used as a transplant method.The results showed that the overall effective rate of fecal bacteria transplantation for ulcerative colitis was 77.78%,the clinical remission rate was 55.56%,the mucosal healing rate was 50%.Moreover,for hormone-dependent patients with therapeutic response could be successfully removed and maintain long-term remission.The incidence of adverse reactions is low,and no serious adverse reactions wasoccured.Inaddition,further analysis of the intestinal flora among donor,response and non-response showed that after transplantation,the intestinal flora structure of the response was close to the donor,and the significantly change occured 1 week after transplantation.The beneficial bacteria(such as Prevotella9,Phascolarctobacterium.Pseudomonas,etc.)increased,while the pathogenic bacteria(Escherichia-Shigella,Parasutterella,Vesococcus,etc.)decreased,of which the change in the non-responsewere not obvious.The increase of Alloprevotella and the decrease of Escherichia-Shigella in FMT-response group may predict the effectiveness of transplantation.Compared with non-response,the composition of the intestinal flora was significantly different from that of the donor in response before transplantation,suggesting that donor with a larger difference in the composition of the intestinal flora from the patient may improve the success rate of transplantation.The serum metabolomics test showed that the metabolites such as taurochenodeoxycholate and taurocholate significantly increased after transplantation,and the KEGG pathway predicted a significant change in bile acid-related metabolism.The correlation analysis between the differential metabolites and the differential flora showed that the bile acid-related metabolites were positively correlated with the abundance of Alloprevotella and Prevotella9.These results suggest that the increase of Alloprevotella after fecal bacteria transplantation intestinal transplantationmay be able to treat ulcerative colitis by regulating bile acid metabolism,improving mucosal permeability and regulating immunity.In additon.animal experiments have proved that fecal microbiota transplantation did have the effect of treating ulcerative colitis and reducing intestinal mucosal permeability.In summary,this topic clarifies that patients of Crohn’s disease and ulcerative colitis do have intestinal flora disorders,and describe specific changes in community structure,reveals the characteristic differential flora in the diagnosis of Crohn’s disease and ulcers.It is proved that the treatment of ulcerative colitis by fecal bacteria transplantation through FMT capsule is a safe,feasible and effective method,and its curative effect is closely related to intestinal flora reconstruction and bile acid metabolism.
Keywords/Search Tags:Crohn’s disease, ulcerative colitis, intestinal flora, serum metabolomics test, fecal bacteria transplantation
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