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Clinical Effect Of Fecal Microbiota Transplantation On Ulcerative Colitis And Construction Of Microbial Markers In Chronic Kidney Patients

Posted on:2021-04-10Degree:MasterType:Thesis
Country:ChinaCandidate:X F DangFull Text:PDF
GTID:2404330605468942Subject:Clinical laboratory diagnostics
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BackgroundThere are very complex microbiome in the human body.Microorganisms colonize various parts of the body such as the intestinal tract,respiratory tract,and urogenital tract.There are more than 1014 microorganisms in the human gastrointestinal tract,and its genetic material is 100 times more than the human genome.The intestinal microbiome is considered to be an active "organ" closely related to the health of the host.The microbiome is an integral part of human genetics.They can prevent pathogen invasion,activate our immune cells,promote various metabolic functions,and directly or indirectly affect most of our physiological functions through these basic functions.Ulcerative colitis(UC)is a type of chronic inflammatory bowel disease(IBD).The main symptom is the recurrence and remission of pus and blood stool.The etiology and pathogenesis of UC are complex,and it is thought to be caused by the imbalance between intestinal flora and mucosal immunity,which leads to excessive inflammation.Therefore,intestinal micro-ecology disorder is considered to be the pathogenesis of UC.Even if the imbalance of intestinal micro-ecology is not the main cause of intestinal mucosa deterioration,it is still a potential cause of intestinal mucosal inflammation,or at least acts as an enhancer.Fecal microbiota transplantation(FMT)refers to the transfer of fecal microbial flora from healthy people into the intestines of patients.This has become a new method to change the gut microbiome and has been successfully applied for treating refractory clostridia infection(CDI).FMT can reverse dysbiosis by increasing the diversity of the gut microbiota and restoring the lost beneficial bacteria.Studies have shown that probiotics can also improve the immune system and intestinal mucosal barrier function,correct intestinal microecological disorders,promote the secretion of anti-inflammatory factors,and inhibit the growth of harmful bacteria.Chronic kidney disease(CKD)is a global health problem.It is one of the common complications of metabolic diseases including obesity and type ? diabetes.More and more studies have shown that bacterial metabolites,such as phenol,indole and amine,may cause uremic toxicity.Patients with end-stage renal disease show an increase in the bacterial family with urease,uricase,indole and p-cresol forming enzymes,while the family with butyrate forming enzymes decreases.Our research group used 16SrRNA gene sequencing method to study the difference of intestinal flora between chronic kidney disease group and normal healthy people group in the preliminary experiment.The study found that at the genus level,12 systemic types in the CKD group were too high,and 19 systemic types in the normal group were too high.The study also found that Holdemanella,Megamonas,Dielma and Scardovia,Anaerofustis genus are associated with the progress of CKD and hemodialysis.Purposes1.Through meta-analysis to understand the effect of FMT and mixed probiotics VSL#3 in relieving ulcerative colitis.2.Through the summary of cases of fecal microbiota transplantation in patients with moderate to severe ulcerative colitis,understand the role of FMT in inducing clinical remission in patients with moderate to severe UC.3.According to the 16SrRNA sequencing results of intestinal microbial changes in patients with renal failure in previous studies,design meaningful bacterial genomic DNA-specific primers,establish microbial markers,and extract DNA from patients 'feces through simple PCR experiments to evaluation the condition of patients with kidney disease and to achieve the purpose of early detection and early intervention.Methods1.According to the first report of the systematic review and meta-analysis(PRISMA)statement,the efficacy and safety of fecal microbiota transplantation and mixed probiotics in the treatment of ulcerative colitis were analyzed.2.We prepared fecal extracts from four donors for infusion.The volume of each infusion is 90 mL.The ulcerative colitis disease activity index(UCDAI)was used to assess the condition of patients after FMT.The simple clinical colitis activity index(SCCAI)was used to assess the patient's condition and quality of life at weeks 1,6,12,and 52 of the first stool transplantation.3.We selected 30 healthy control group(HC)population and 95 chronic kidney disease group(CKD)patients according to whether hemodialysis is divided into three groups:healthy control group 30 cases,chronic kidney disease non-dialysis group(CKD-NonHD)Stool samples from 34 patients and 61 patients in the chronic kidney disease dialysis group(CKD-HD)were numbered.After the DNA extracted using the stool DNA extraction kit,real-time fluorescence quantitative PCR and ordinary PCR were used to determine the three intestinal bacteria in the stool DNA and analyze the specificity and sensitivity of the detection method.Results1.Seven randomized,double-blind,placebo-controlled trials were used as the source of induced remission data.FMT and probiotic treatments were superior to placebo Indirect comparisons revealed that FMT and probiotic VSL#3 did not reach statistics in clinical response(RR=1.20,95%CI=0.70-2.06)or clinical response(RR=0.95,95%CI=0.62-1.45).In terms of safety,there was no statistically significant increase in FMT and VSL#3.In terms of serious adverse events,there was no statistical difference between the FMT group and the control group.The probiotic VSL#3 appears to be safer than FMT,because no serious adverse events have been reported in the VSL#3 article2.Of the 12 patients with moderate to severe ulcerative colitis who underwent repeated FMT,11 patients achieved clinical remission,and 5 patients were still in clinical remission at 52 weeks of follow-up;6 patients relapsed within 52 weeks;only one patient did not respond to FMT.Four patients received FMT after relapse,but reapplying FMT did not achieve the expected results.In addition,all patients had good compliance,and no adverse events were observed after FMT during follow-up3.The positive rate of three enterobacteriaceae for the combined diagnosis of uremic patients was 73.8%,the positive rate for the combined diagnosis of non-dialysis patients with CKD was 30.8%,and the positive rate for the combined diagnosis of total CKD patients was 62.1%Conclusions1.Fecal bacteria transplantation or mixed probiotic VSL#3 has achieved good results in clinical remission and clinical response of active ulcerative colitis,and did not increase the risk of adverse reactions.The therapeutic effect of FMT was not statistically different from that of mixed probiotic VSL#3.2.Multiple consecutive FMT is effective and safe for patients with moderate to severe UC.However,double-blind,randomized controlled trials and better methods are needed to understand why FMT is not effective after relapse.3.Compared with healthy people,the structure of intestinal flora of patients with chronic kidney disease has changed.Scardovia,Dielma,Anaerofustis can be used as microbial markers for patients with chronic kidney disease.
Keywords/Search Tags:Fecal microbiota transplantation, ulcerative colitis, probiotics, chronic kidney disease, intestinal flora, microbial markers
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