FMT Evidence

Fecal Microbiota Transplantation (FMT) is an investigational treatment that offers great promise.  FMT involves transplanting carefully screened, processed stool from a healthy donor into a sick patient’s colon.  Researchers have observed FMT to be as much as 90% effective for the treatment of recurrent C. difficile, a potentially deadly gastrointestinal infection. 

Based on the currently available body of evidence of FMT for recurrent C. difficile, medical professional societies have advocated for FMT as standard of care for patients with this infection. A summary of the results of FMT studies for recurrent C. difficile can be found in Table 1, below. Given this body of evidence and the lack of viable alternative options for patients, the FDA has allowed clinicians to provide FMT to recurrent C. difficile patients outside of clinical trials.

In addition to the available research on FMT for recurrent C. difficile, promising results in ulcerative colitis and other disease areas (summarized in Table 2 below) further support the ongoing investigation of FMT. As the field matures, ongoing research should, and will, continue to explore the safety and efficacy of FMT for C. difficile and other diseases. We look forward to supporting the network of researchers exploring these questions. 

Table 1: Summary of FMT studies for recurrent C. difficile infection

References Randomized Trials 1.     Kelly, C., Khoruts, A., Staley, C., et al. 2016. Effect of fecal microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection: a randomized trial. Annals of Internal Medicine 165 (9): 609-616. 2.     Lee CH, Steiner T, Petrof EO, et al. Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent Clostridium difficile infection: a randomized clinical trial. JAMA 2016;315(2):142–9. 3.     Cammarota G, Masucci L, Ianiro G, et al. Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther 2015;41(9):835–43. 4.     Youngster I, Sauk J, Pindar C, et al. Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study. Clin Infect Dis 2014;58(11):1515–22. 5.     van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. N Engl J Med 2013;368(5):407–15. Systematic reviews 1.     Drekonja D, Reich J, Gezahegn S, et al. Fecal microbiota transplantation for Clostridium difficile infection: A systematic review. Ann Intern Med 2015;162(9):630–8. 2.     Kassam Z, Lee CH, Yuan Y, Hunt R. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol 2013;108(4): 500–508. Cohort studies 1.     O’Brien K, Osman M, Eysenbach L, et al. Clinical efficacy of fecal microbiota transplantation for recurrent Clostridium difficile infection from an international public stool bank: results from a 1,406 patient multi-center cohort. Digestive Disease Week 2016 Available from: http://linkinghub.elsevier.com/retrieve/pii/S0016508516318546 Oral delivery modality 1.     Fischer M, Allegretti JR, Smith M, et al. A multi-center, cluster randomized dose-finding study of fecal microbiota transplantation capsules for recurrent Clostridium difficile infection. UEGW 2016. 2.     Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA 2014;312(17):1772–8. 3.     Hirsch BE, Saraiya N, Poeth K, Schwartz RM, Epstein ME, Honig G. Effectiveness of fecal-derived microbiota transfer using orally administered capsules for recurrent Clostridium difficile infection. BMC Infect Dis 2015;15:191.

References

Randomized Trials

1.     Kelly, C., Khoruts, A., Staley, C., et al. 2016. Effect of fecal microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection: a randomized trial. Annals of Internal Medicine 165 (9): 609-616.

2.     Lee CH, Steiner T, Petrof EO, et al. Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent Clostridium difficile infection: a randomized clinical trial. JAMA 2016;315(2):142–9.

3.     Cammarota G, Masucci L, Ianiro G, et al. Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther 2015;41(9):835–43.

4.     Youngster I, Sauk J, Pindar C, et al. Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study. Clin Infect Dis 2014;58(11):1515–22.

5.     van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. N Engl J Med 2013;368(5):407–15.

Systematic reviews

1.     Drekonja D, Reich J, Gezahegn S, et al. Fecal microbiota transplantation for Clostridium difficile infection: A systematic review. Ann Intern Med 2015;162(9):630–8.

2.     Kassam Z, Lee CH, Yuan Y, Hunt R. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol 2013;108(4): 500–508.

Cohort studies

1.     O’Brien K, Osman M, Eysenbach L, et al. Clinical efficacy of fecal microbiota transplantation for recurrent Clostridium difficile infection from an international public stool bank: results from a 1,406 patient multi-center cohort. Digestive Disease Week 2016 Available from: http://linkinghub.elsevier.com/retrieve/pii/S0016508516318546

Oral delivery modality

1.     Fischer M, Allegretti JR, Smith M, et al. A multi-center, cluster randomized dose-finding study of fecal microbiota transplantation capsules for recurrent Clostridium difficile infection. UEGW 2016.

2.     Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA 2014;312(17):1772–8.

3.     Hirsch BE, Saraiya N, Poeth K, Schwartz RM, Epstein ME, Honig G. Effectiveness of fecal-derived microbiota transfer using orally administered capsules for recurrent Clostridium difficile infection. BMC Infect Dis 2015;15:191.

Table 2: Summary of FMT studies in disease areas outside recurrent C. difficile

Table 2 References Ulcerative Colitis 1.     Paramsothy S, Kamm MA, Walsh A, et al. Multi donor intense faecal microbiota transplantation is an effective treatment for resistant ulcerative colitis: a randomised placebo-controlled trial. Gastroenterology 2016;150(4):S122–3. 2.     Moayyedi P, Surette MG, Kim PT, et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 2015;149(1):102–9.e6. 3.     Rossen NG, Fuentes S, van der Spek MJ, et al. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology 2015;149(1):110–8.e4. Metabolic Syndrome 1.     Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 2012;143(4):913–6.e7. Graft vs. Host Disease 1.     Kakihana K, Fujioka Y, Suda W, et al. Fecal microbiota transplantation for patients with steroid-resistant/dependent acute graft-versus-host disease of the gut. Blood 2016;blood– 2016–05 – 717652.

Table 2 References

Ulcerative Colitis

1.     Paramsothy S, Kamm MA, Walsh A, et al. Multi donor intense faecal microbiota transplantation is an effective treatment for resistant ulcerative colitis: a randomised placebo-controlled trial. Gastroenterology 2016;150(4):S122–3.

2.     Moayyedi P, Surette MG, Kim PT, et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 2015;149(1):102–9.e6.

3.     Rossen NG, Fuentes S, van der Spek MJ, et al. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology 2015;149(1):110–8.e4.

Metabolic Syndrome

1.     Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 2012;143(4):913–6.e7.

Graft vs. Host Disease

1.     Kakihana K, Fujioka Y, Suda W, et al. Fecal microbiota transplantation for patients with steroid-resistant/dependent acute graft-versus-host disease of the gut. Blood 2016;blood– 2016–05 – 717652.