The science is in.
To date more than 6,000 scientific articles have been published on the GI microbiome and more than 600 have been published related to FMT. Ongoing studies are in place to continue unraveling the intricacies of the microbiota inhabiting the GI tract.
The application of FMT has been extensively reviewed in published scientific journals. Several selected surveys and trial articles are presented below:
01Fecal microbiota transplant in patients with Clostridium difficile infection: A systematic review.
RESULTS: Retrospective and uncontrolled prospective cohort studies suggest that FMT is a highly effective therapy for recurrent/refractory CDI, with clinical success rates ranging from 83% to 100%, which is similar to rates published by two randomized controlled trials.
02Fecal Microbiota Transplantation for Clostridium difficile Infection A Systematic Review.
RESULTS: Two randomized, controlled trials (RCTs); 28 case-series studies; and 5 case reports were included. Two RCTs and 21 case-series studies (516 patients receiving FMT) reported using FMT for patients with recurrent CDI. Across all studies for recurrent CDI, symptom resolution was seen in 85% of cases.
01Update on FMT 2015: Indications, Methodologies, Mechanisms and Outlook
The community of microorganisms within the human gut (or microbiota) is critical to health and functions with a level of complexity comparable to an organ system. Alterations of this ecology (or dysbiosis) has been implicated in a number of disease states, the prototypical example being Clostridium difficile infection (CDI). Fecal microbiota transplantation (FMT) has been demonstrated to durably alter the gut microbiota of the recipient and has shown efficacy in the treatment of recurrent CDI. There is hope that FMT may eventually prove beneficial for treatment of other disease associated with alterations in gut microbiota, such as inflammatory bowel disease, irritable bowel syndrome and the metabolic syndrome, to name a few. Although the basic principles that underlie the mechanisms by which FMT demonstrates therapeutic efficacy in CDI are becoming apparent, further research is needed to understand the possible role of FMT in these other conditions. Though relatively simple to perform, questions regarding both short- and long-term safety, as well as the complex and rapidly evolving regulatory landscape has limited widespread utilization. Future work will focus on establishing best practices and more robust safety data than exist currently, as well as refining FMT beyond current “whole stool” transplants to increase safety and tolerability. Encapsulated formulations, full spectrum stool-based products and defined microbial consortia are all in the immediate future.
02Fecal Microbiota Transplantation: Indications, Methods, Evidence, and Future Directions
Fecal microbiota transplantation (FMT) has attracted great interest in recent years, largely due to the global Clostridium difficile infection (CDI) epidemic and major advances in metagenomic sequencing of the gastrointestinal (GI) microbiota, with growing understanding of its structure and function. FMT is now recommended as the most effective therapy for relapsing CDI and, with further refinement, may even be used in “first-time” CDI. There is interest also in other conditions related to GI dysbiosis—for example, inflammatory bowel disease, irritable bowel syndrome, obesity, and diabetes mellitus—although quality evidence is at present lacking. A few trials are now underway in FMT for ulcerative colitis. Many unanswered questions remain, including FMT methodology—for example, optimal route of administration, what makes a “good donor,” safety issues, and long-term effects of FMT.
01Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial.
From November, 2013, to May, 2015, 85 patients were enrolled to our trial, of whom 42 were randomly assigned faecal microbiota transplantation and 43 were allocated placebo. One patient assigned faecal microbiota transplantation and three allocated placebo did not receive study treatment and were excluded from the analysis. The primary outcome was achieved in 11 (27%) of 41 patients allocated faecal microbiota transplantation versus three (8%) of 40 who were assigned placebo (risk ratio 3·6, 95% CI 1·1-11·9; p=0·021). Adverse events were reported by 32 (78%) of 41 patients allocated faecal microbiota transplantation and 33 (83%) of 40 who were assigned placebo; most were self-limiting gastrointestinal complaints, with no significant difference in number or type of adverse events between treatment groups. Serious adverse events occurred in two patients assigned faecal microbiota transplantation and in one allocated placebo. Microbial diversity increased with and persisted after faecal microbiota transplantation. Several bacterial taxa were associated with clinical outcome; in particular, the presence of Fusobacterium spp was associated with lack of remission.
02Fecal Microbiota Transplantation as Therapy for Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.
Results: Eighteen studies (9 cohort studies, 8 case studies and 1 randomized controlled trial) were included in the analysis. 122 patients were described (79 ulcerative colitis (UC); 39 Crohn’s disease (CD); 4 IBD unclassified). Overall, 45% (54/119) of patients achieved CR during follow up
03Fecal Microbiota Transplantation is Safe and Efficacious for Recurrent or Refractory Clostridium difficile Infection in Patients with Inflammatory Bowel Disease.
RESULTS: Sixty-seven patients were included in the analysis. Thirty-five (52%) had Crohn’s disease, 31 (46%) ulcerative colitis, and one indeterminate colitis with 43 (64%) patients on an immunosuppressive agent at the time of FMT. The initial FMT was successful in 53 (79%) patients. After the FMT, IBD disease activity was reported as improved in 25 (37%), no change in 20 (30%), and worse in 9 (13%) patients.
04Fecal microbiota transplantation through mid-gut for refractory Crohn's disease: safety, feasibility, and efficacy trial results
Results: Metagenomics analysis showed a high concordance between feces sample and purified fecal microbiota from same donors. Standardized fecal microbiota preparation and clinical flow significantly simplified the practical aspects of FMT. Totally, 30 patients were qualified for the present analysis. The rate of clinical improvement and remission based on clinical activity at the first month was 86.7% (26/30) and 76.7% (23/30), respectively, which was higher than other assessment points within 15-month follow-up. Patients’ body weight increased after FMT, and the lipid profile improved as well. FMT also showed a fast and continuous significant effect in relieving the sustaining abdominal pain associated with sustaining CD.
01Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.
MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks).
02Fecal microbiota transplantation in patients with slow-transit constipation: A randomized, clinical trial
Fecal microbiota transplantation has been proposed as a therapeutic approach for chronic constipation. This randomized, controlled trial aimed to compare the effects of conventional treatment alone (control) with additional treatment with FMT (intervention) in patients with slow-transit constipation (STC). Adults with STC were randomized to receive intervention or control treatment. The control group received education, behavioral strategies, and oral laxatives. The intervention group was additionally provided 6 days of FMT. The primary endpoint was the clinical cure rate (proportion of patients achieving a mean of ≥ three complete spontaneous bowel movements [CSBMs] per week]. Secondary outcomes and safety parameters were assessed throughout the study. Sixty patients were randomized to either conventional treatment alone (n = 30) or FMT (n = 30) through a nasointestinal tube. There were significant differences between the intervention group and control group in the clinical improvement rate (intention-to-treat [ITT]: 53.3% vs. 20.0%, P = 0.009), clinical cure rate (ITT: 36.7% vs. 13.3%, P = 0.04), mean number of CSBMs per week (ITT: 3.2 ± 1.4 vs. 2.1 ± 1.2, P = 0.001), and the Wexner constipation score (ITT: 8.6 ± 1.5 vs. 12.7 ± 2.5, P < 0.00001). Compared with the control group, the intervention group showed better results in the stool consistency score (ITT: 3.9 vs. 2.4, P < 0.00001) and colonic transit time (ITT: 58.5 vs. 73.6 h, P < 0.00001). The intervention group had more treatment-related adverse events than did the control group (50 vs. 4 cases). FMT was significantly more effective (30% higher cure rate) for treatment of STC than conventional treatment. No serious adverse events were observed.
01Fecal Microbiota Transplantation: Current Applications, Effectiveness, and Future Perspectives
02Step-up fecal microbiota transplantation (FMT) strategy
03Fecal microbial transplant for the treatment of pediatric inflammatory bowel disease
04Fecal microbiota transplantation through mid-gut for refractory Crohn’s disease: safety, feasibility, and efficacy trial results.
05Fecal Microbiota Transplantation: Expanding Horizons for Clostridium difficile Infections and Beyond
06Fecal Microbial Transplants Reduce Antibiotic-resistant Genes in Patients With Recurrent Clostridium difficile Infection
Further Clinical Research in Asia
The Asia Microbiota Bank is here to help investigators uncover the role of the gut microbiome in human health, and to discover how engineering it can drive better health outcomes. AMB seeks to partner with passionate clinical researchers, combining their disease area and clinical expertise with our extensive knowledge of the microbiome and fecal microbiota transplantation (FMT) to shape the future of microbial therapies.
Today, AMB is in the planning and development stage of more than four FMT trials across a broad array of indications. We invite you to join us and other thought leaders in the field as part of our growing network of collaborators.