Fecal Microbiota and Human Intestinal Fluid Transplantation: Methodologies and Outlook.

Fecal microbiota transplantation (FMT) is a therapy that involves the transplantation of healthy human fecal microorganisms into the gut of patients to rebuild or consolidate the intestinal microecology. It has been utilized in many diseases. However, FMT had a limited effect on patients with small intestinal diseases because of the unique ecological characteristics of the microorganisms. Thus, we proposed a new microecology transplantation therapy called human intestinal fluid transplantation (HIFT). Human intestinal fluid can be collected through a nasojejunal tube and be made into capsules using the freeze-dried powder method. In addition, strict standards for donor screening and management have been established. We are currently developing a high-standard HIFT preparation system and conducting high-quality clinical studies to validate the safety and efficacy of HIFT combined with FMT.

FTACMT study protocol: a multicentre, double-blind, randomised, placebo-controlled trial of faecal microbiota transplantation for autism spectrum disorder.

INTRODUCTION: Autism spectrum disorder (ASD) is a complicated diffuse developmental disorder that commonly involves gastrointestinal distress and dysbacteriosis. Emerging lines of evidence have shown faecal microbiota transplantation (FMT) to be a potential therapeutic strategy for improving the clinical outcomes of patients with ASD by re-establishing their intestinal microflora. We are undertaking the first-ever multicentre, double-blind, randomised controlled trial of FMT for the treatment of children with both ASD and gastrointestinal symptoms and will assess the feasibility and efficacy outcomes of this strategy. METHODS: In total, 318 children with both ASD and gastrointestinal symptoms will be enrolled (from 15 hospitals in China) to receive either FMT intervention (n=212) or a placebo (control, n=106). Children aged 3-6 years will take two capsules two times a day, and those older than 6 years will take three capsules two times a day. Each patient will receive four treatment courses, with each 12-day course being repeated every month. Outcomes will be evaluated at baseline, throughout the period of intervention, and at subsequent follow-ups for 2 months. The primary trial objective is to investigate the remodelling effect of FMT on the intestinal microflora in patients with ASD. The secondary objective focuses on the clinical efficacy and safety of FMT, including its improvement of the clinical response and metabonomics. ETHICS AND DISSEMINATION: Ethical approval was obtained from the hospital Ethics Committee of each Faecal Transfer for ASD China Multicenter Trial Working Group. The ongoing FMT clinical trial is intended to support the approval of the new technology and its administration. The results of this trial will provide high-quality evidence to inform the future clinical application of this new therapy. TRIAL REGISTRATION NUMBER: ChiCTR2100043906; Pre-results.

A five-year follow-up analysis of efficacy and complications of 3 932 cases of fecal microbiota transplantation treatment / 中华消化杂志

Objective:To observe the long-term efficacy and complication rate of fecal microbiota transplantation (FMT) and the effects of different ways of transplantation and treatment courses on the efficacy of FMT.Methods:From April 2012 to April 2020, the data of 3 932 patients (804 cases of Nanjing General Hospital of Nanjing Military Command and 3 128 cases of Tenth People′s Hospital of Tongji University) who voluntarily received FMT treatment were prospectively collected. After the first course of transplantation, the follow-up rate and efficacy and complications in 5 years were observed at the 1st, 12th, 24th, 36th, 48th and 60th month. According to the different ways of the first transplantation, 3 932 patients were divided into nasointestinal tube group (2 604 cases), capsule group (873 cases), colonoscopy group (268 cases) and enema group (187 cases). One month after transplantation, the effective rate and complication were observed. At the same time, the 1 813 patients with FMT less than four courses were divided into 1 treatment course group (369 cases), 2 treatment courses group (568 cases), 3 treatment courses group (497 cases) and 4 treatment courses group (379 cases). The effective rates of patients in four groups with different treatment courses were observed 6 months after finishing the treatment. Chi square test was used for statistical analysis.Results:Among 3 932 patients, the follow-up rates at 1st, 12th, 24th, 36th, 48th and 60th month after the first course of FMT were 93.67%(3 683/3 932), 82.30%(2 307/2 803), 82.17%(1 825/2 221), 62.41%(978/1 567), 59.85%(559/934) and 60.84%(289/475), respectively. The total effective rates at 1st, 12th, 24th, 36th, 48th and 60th month were 67.23%(2 476/3 683), 64.20%(1 481/2 307), 59.29%(1 082/1 825), 59.71%(584/978), 55.81%(312/559) and 59.17%(171/289), respectively. During FMT period, the total incidence of different complications was 34.49%(1 356/3 932). During follow-up period, the total rate of complication was 4.22%(166/3 932). There were no serious adverse events such as gastrointestinal perforation, multi-drug resistant bacterial infection, organ failure and death. One month after FMT, the effective rates of nasojejunal tube group, capsule group, colonoscopy group, and enema group were 67.18%(1 668/2 483), 68.63%(549/800), 67.23%(158/235), 61.21%(101/165), respectively. There was no significant difference among the four groups ( P>0.05). The effective rates of patients with chronic constipation in nasal jejunal tube group, capsule group and colonoscopy group were all higher than that of enema group (67.82%, 1 043/1 538; 67.98%, 138/203 and 62.96%, 17/27 vs. 26.67%, 8/30), and the differences were statistically significant ( χ2=22.55, 19.07 and 7.60, all P<0.01). During the period of FMT, the total incidence of complications of nasojejunal tube group, capsule group, colonoscopy group and enema group were 35.22%(917/2 604), 30.24%(264/873), 42.54%(114/268) and 32.62%(61/187), respectively. The difference was statistically significant among four groups ( χ2 =18.84, P<0.01). Among nasojejunal tube group, capsule group, colonoscopy group and enema group, there were significant differences in the incidence of diarrhea (4.49%, 117/2 604; 4.58%, 40/873; 7.83%, 21/268 and 5.35%, 10/187, respectively), throat pain (5.30%, 138/2 604; 0.69%, 6/873; 2.99%, 8/268 and 1.07%, 2/187, respectively), gastrointestinal bleeding (0; 0; 1.87%, 5/268 and 0.53%, 1/187, respectively) and enterogenous infection (0; 0; 1.49%, 4/268 and 0.53%, 1/187, respectively) ( χ2 =8.24, 39.24, 63.13 and 49.68, all P<0.05). At the 6th month after treatment, the effective rates of 1 treatment course group, 2 treatment courses group, 3 treatment courses group and 4 treatment courses group were 63.94%(211/330), 61.93%(301/486), 65.75%(286/435) and 72.54%(251/346), respectively. There were statistically significant differences among groups with different treatment courses ( χ2 =10.70, P =0.01). The effective rate of the four treatment courses group was significantly higher than those of the one treatment course group, two treatment courses group and three treatment courses group, and the differences were statistically significant ( χ2=5.78, 10.18 and 4.14, all P<0.05). The effective rates of in chronic constipation and autism in 4 treatment courses group were significantly higher than those in 1 treatment course group and 2 treatment courses group (72.73%(136/187) vs.55.47%(71/128) and 58.71%(155/264), 72.73%(40/55) vs.6/15 and 47.83%(11/23)), the effective rate of autism in 3 treatment courses group was higher than that in 1 treatment course group (69.05%(29/42) vs. 6/15), and the differences were statistically significant ( χ2=10.05, 9.39, 5.60, 4.44 and 3.94, all P<0.05). Conclusions:The long-time efficacy of FMT is definite in the treatment of intestinal flora derangement related intestinal diseases and extraintestinal diseases complicated with intestinal disfunction and there are no serious adverse events. The efficacy of FMT is related to the way of transplantation and treatment. The incidence of complications of FMT is related to the way of transplantation. Different ways of transplantation and treatment courses should be formulated for different diseases.