Clinical Study Of Fecal Microbiota Transplantation In The Treatment Of Ulcerative Colitis

Objective:Ulcerative colitis(UC)is a chronic recurrent intestinal disease with unclear pathogenesis.Presently,the treatment of ulcerative colitis is mainly drug therapy.Due to the poor efficacy and many side-effects of drug therapy,it is urgent to explore new safe and effective treatment measures.Studies have shown that the intestinal microbiota disturbance plays a key role in the occurrence and development of ulcerative colitis.Intestinal microbiota transplantation(IMT),also known as fecal microbiota transplantation(FMT),treating intestinal and external diseases by transplanting functional microbiota from healthy human feces into patients,to improve/rebuild intestinal microbiota and treat intestinal diseases.However,the safety and efficacy of FMT in the treatment of UC remain controversial,and the mechanism of action has not yet been clarified.The purpose of this study was to evaluate the clinical effect and safety of FMT in the treatment of UC,and to explore the relevant mechanism of intestinal microbiota disorder in the pathogenesis of UC.Methods A total of 15 patients with UC who were admitted to the First Affiliated Hospital of Anhui Medical University from April 2018 to June 2019,who are not responding to mesalamine therapy or who are hormonally resistant and dependent,were selected to receive multi-donor FMT treatment once every other day for total 3 times.The change of Mayo score,CRP,ESR,IL-6,IL-10,TNF-? and fecal calprotectin before and 6 weeks after treatment were observed.16 Sr RNA sequencing was used to detect changes in intestinal microbiota before and after treatment.Before and after FMT,the colonoscopy and endoscopic Mayo score was performed.With reference to the literature,the response rate of intestinal microbiota transplantation was defined as the total Mayo score decreased by ?3 points and the therapeutic remission rate was defined as the total Mayo score ?2 points and the endoscopic Mayo score ?1 point.Results The response rate was 61.5% and the remission rate was 46.1% in 13 patients 6weeks after transplantation.The Mayo score of patients after treatment was significantly lower than that before FMT treatment(P < 0.01).CRP,ESR,IL-6,IL-10 and TNF-?had no obvious change before and after treatment,but fecal calprotectin decreased significantly(P < 0.01).After FMT the diversity of intestinal microbiota in patients remarkably increased,and the composition of intestinal microbiota was significantly changed.The contents of several species of intestinal pro-inflammatory bacteria were evidently decreased,and the contents of Dialister related to intestinal anti-inflammatory bacteria were significantly increased.LEf SE,STAMP differential metabolic pathway analysis shows that there were significant differences in the composition of metabolic pathways before and after transplantation,such as significantly increased polyammonia biosynthesis superpathway II and significantly decreased vitamin K and enterobacterial common antigen synthesis pathway.After treatment,the Mayo endoscopy score of the patients decreased significantly(P < 0.01).No serious adverse reactions were found in the study.Conclusions After FMT,Patients' disease activity score,endoscopy score and fecal calprotectin decreased significantly,as well as intestinal microbiota diversity increased significantly. FMT is safe and effective in patients with active UC who are not responding to mesalamine therapy or who are hormonally resistant and dependent.