Clin Endosc.  2019 Mar;52(2):137-143. 10.5946/ce.2019.009.

Fecal Microbiota Transplantation: An Update on Clinical Practice

• Kim KO
• Gluck M

• KMID: 2447670
• DOI: http://doi.org/10.5946/ce.2019.009

Abstract

Fecal microbiota transplantation (FMT) is an infusion in the colon, or the delivery through the upper gastrointestinal tract, of stool from a healthy donor to a recipient with a disease believed to be related to an unhealthy gut microbiome. FMT has been successfully used to treat recurrent Clostridium difficile infection (rCDI). The short-term success of FMT in rCDI has led to investigations of its application to other gastrointestinal disorders and extra-intestinal diseases with presumed gut dysbiosis. Despite the promising results of FMT in these conditions, several barriers remain, including determining the characteristics of a healthy microbiome, ensuring the safety of the recipient with respect to long-term outcomes, adequate monitoring of the recipient of fecal material, achieving high-quality control, and maintaining reasonable costs. For these reasons, establishing uniform protocols for stool preparation, finding the best modes of FMT administration, maintaining large databases of donors and recipients, and assuring that oral ingestion is equivalent to the more widely accepted colonoscopic infusion are issues that need to be addressed.

Keyword

Fecal microbiota transplantation; Clostridium difficile infection; Colonoscopy

MeSH Terms

Clostridium difficile
Clothing
Colon
Colonoscopy
Dysbiosis
Eating
Fecal Microbiota Transplantation*
Gastrointestinal Microbiome
Humans
Microbiota
Tissue Donors
Upper Gastrointestinal Tract

Reference

1. Eiseman B, Silen W, Bascom GS, Kauvar AJ. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958; 44:854–859.

2. Chin SM, Sauk J, Mahabamunuge J, Kaplan JL, Hohmann EL, Khalili H. Fecal microbiota transplantation for recurrent Clostridium difficile infection in patients with inflammatory bowel disease: a single-center experience. Clin Gastroenterol Hepatol. 2017; 15:597–599.

3. Bakken JS, Borody T, Brandt LJ, et al. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol. 2011; 9:1044–1049.

4. Brandt LJ, Aroniadis OC. An overview of fecal microbiota transplantation: techniques, indications, and outcomes. Gastrointest Endosc. 2013; 78:240–249.

5. Gerding DN. Metronidazole for Clostridium difficile-associated disease: is it okay for Mom? Clin Infect Dis. 2005; 40:1598–1600.

6. Wenisch C, Parschalk B, Hasenhundl M, Hirschl AM, Graninger W. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea. Clin Infect Dis. 1996; 22:813–818.

7. Sadowsky MJ, Khoruts A. Faecal microbiota transplantation is promising but not a panacea. Nat Microbiol. 2016; 1:16015.

8. Choi HH, Cho YS. Fecal microbiota transplantation: current applications, effectiveness, and future perspectives. Clin Endosc. 2016; 49:257–265.

9. Cammarota G, Ianiro G, Gasbarrini A. Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review. J Clin Gastroenterol. 2014; 48:693–702.

10. Kelly CR, Khoruts A, Staley C, et al. Effect of fecal microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection: a randomized trial. Ann Intern Med. 2016; 165:609–616.

11. van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013; 368:407–415.

12. 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; 58:1515–1522.

13. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013; 108:478–498. quiz 499.

14. Trubiano JA, Cheng AC, Korman TM, et al. Australasian Society of Infectious Diseases updated guidelines for the management of Clostridium difficile infection in adults and children in Australia and New Zealand. Intern Med J. 2016; 46:479–493.

15. McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018; 66:987–994.

16. Quraishi MN, Widlak M, Bhala N, et al. Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection. Aliment Pharmacol Ther. 2017; 46:479–493.

17. Moayyedi P, Yuan Y, Baharith H, Ford AC. Faecal microbiota transplantation for Clostridium difficile-associated diarrhoea: a systematic review of randomised controlled trials. Med J Aust. 2017; 207:166–172.

18. Fischer M, Sipe B, Cheng YW, et al. Fecal microbiota transplant in severe and severe-complicated Clostridium difficile: a promising treatment approach. Gut Microbes. 2017; 8:289–302.

19. Kelly CR, Kahn S, Kashyap P, et al. Update on fecal microbiota transplantation 2015: indications, methodologies, mechanisms, and outlook. Gastroenterology. 2015; 149:223–237.

20. Cammarota G, Ianiro G, Tilg H, et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017; 66:569–580.

21. Vindigni SM, Surawicz CM. Fecal microbiota transplantation. Gastroenterol Clin North Am. 2017; 46:171–185.

22. Zhang SL, Wang SN, Miao CY. Influence of microbiota on intestinal immune system in ulcerative colitis and its intervention. Front Immunol. 2017; 8:1674.

23. Costello SP, Soo W, Bryant RV, Jairath V, Hart AL, Andrews JM. Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis. Aliment Pharmacol Ther. 2017; 46:213–224.

24. Paramsothy S, Kamm MA, Kaakoush NO, et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet. 2017; 389:1218–1228.

25. Vindigni SM, Zisman TL, Suskind DL, Damman CJ. The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions. Therap Adv Gastroenterol. 2016; 9:606–625.

26. Khoruts A, Rank KM, Newman KM, et al. Inflammatory bowel disease affects the outcome of fecal microbiota transplantation for recurrent Clostridium difficile infection. Clin Gastroenterol Hepatol. 2016; 14:1433–1438.

27. Newman KM, Rank KM, Vaughn BP, Khoruts A. Treatment of recurrent Clostridium difficile infection using fecal microbiota transplantation in patients with inflammatory bowel disease. Gut Microbes. 2017; 8:303–309.

28. Khanna S, Shin A, Kelly CP. Management of Clostridium difficile infection in inflammatory bowel disease: expert review from the clinical practice updates committee of the AGA institute. Clin Gastroenterol Hepatol. 2017; 15:166–174.

29. Johnsen PH, Hilpüsch F, Cavanagh JP, et al. Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial. Lancet Gastroenterol Hepatol. 2018; 3:17–24.

30. Zhou D, Pan Q, Shen F, et al. Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota. Sci Rep. 2017; 7:1529.

31. Bajaj JS, Kassam Z, Fagan A, et al. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: a randomized clinical trial. Hepatology. 2017; 66:1727–1738.

32. Jayasinghe TN, Chiavaroli V, Holland DJ, Cutfield WS, O’Sullivan JM. The new era of treatment for obesity and metabolic disorders: evidence and expectations for gut microbiome transplantation. Front Cell Infect Microbiol. 2016; 6:15.

33. Ruggiero M. Fecal microbiota transplantation and the brain microbiota in neurological diseases. Clin Endosc. 2016; 49:579.

34. Kelly CR, Ihunnah C, Fischer M, et al. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol. 2014; 109:1065–1071.

35. Kelly BJ, Tebas P. Clinical practice and infrastructure review of fecal microbiota transplantation for Clostridium difficile infection. Chest. 2018; 153:266–277.

36. McCune VL, Struthers JK, Hawkey PM. Faecal transplantation for the treatment of Clostridium difficile infection: a review. Int J Antimicrob Agents. 2014; 43:201–206.

37. Brandt LJ. American Journal of Gastroenterology lecture: intestinal microbiota and the role of fecal microbiota transplant (FMT) in treatment of C. difficile infection. Am J Gastroenterol. 2013; 108:177–185.

38. Allegretti JR, Kassam Z, Osman M, Budree S, Fischer M, Kelly CR. The 5D framework: a clinical primer for fecal microbiota transplantation to treat Clostridium difficile infection. Gastrointest Endosc. 2018; 87:18–29.

39. Kim KO, Schwartz M, Gluck M. Reducing cost and scheduling complexity of fecal microbiota transplantation by using universal donor over patients-directed donors in patients with recurrent Clostrodium difficile infections. Gastroenterology. 2018; 154(6 Suppl 1):S191.

40. Edelstein C, Daw JR, Kassam Z. Seeking safe stool: Canada needs a universal donor model. CMAJ. 2016; 188:E431–E432.

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

42. OpenBiome. OpenBiome quality & safety program [Internet]. Cambridge (MA): OpenBiome;c2017. c2017 [updated 2017 May; cited 2018 Apr 26]. Available from: https://www.openbiome.org/safety.

43. 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; 315:142–149.

44. Kazerouni A, Burgess J, Burns LJ, Wein LM. Optimal screening and donor management in a public stool bank. Microbiome. 2015; 3:75.

45. Smith M, Kassam Z, Edelstein C, Burgess J, Alm E. OpenBiome remains open to serve the medical community. Nat Biotechnol. 2014; 32:867.

46. Gerding DN, Lessa FC. The epidemiology of Clostridium difficile infection inside and outside health care institutions. Infect Dis Clin North Am. 2015; 29:37–50.

47. Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011; 53:994–1002.

48. 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; 312:1772–1778.

49. Fischer M, Kao D, Mehta SR, et al. Predictors of early failure after fecal microbiota transplantation for the therapy of Clostridium difficile infection: a multicenter study. Am J Gastroenterol. 2016; 111:1024–1031.

50. Postigo R, Kim JH. Colonoscopic versus nasogastric fecal transplantation for the treatment of Clostridium difficile infection: a review and pooled analysis. Infection. 2012; 40:643–648.

51. Sofi AA, Silverman AL, Khuder S, Garborg K, Westerink JM, Nawras A. Relationship of symptom duration and fecal bacteriotherapy in Clostridium difficile infection-pooled data analysis and a systematic review. Scand J Gastroenterol. 2013; 48:266–273.

52. Obi O, Hampton D, Anderson T, et al. Fecal microbiota transplant for treatment of resistant C. difficile infection using a standardized protocol: a community hospital experience: 2172. Am J Gastroenterol. 2014; 109(Suppl 2):S629.

53. Baxter M, Ahmad T, Colville A, Sheridan R. Fatal aspiration pneumonia as a complication of fecal microbiota transplant. Clin Infect Dis. 2015; 61:136–137.

54. Zipursky JS, Sidorsky TI, Freedman CA, Sidorsky MN, Kirkland KB. Patient attitudes toward the use of fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection. Clin Infect Dis. 2012; 55:1652–1658.

55. Kao D, Roach B, Silva M, et al. Effect of oral capsule- vs colonoscopy-delivered fecal microbiota transplantation on recurrent Clostridium difficile infection: a randomized clinical trial. JAMA. 2017; 318:1985–1993.

56. Allegretti JR, Fischer M, Papa E, et al. Fecal microbiota transplantation delivered via oral capsules achieves microbial engraftment similar to traditional delivery modalities: safety, efficacy and engraftment results from a multi-center cluster randomized dose-finding study. Gastroenterology. 2016; 150(4 Suppl 1):S540.

57. Allegretti JR, Allegretti AS, Phelps E, Xu H, Fischer M, Kassam Z. Classifying fecal microbiota transplantation failure: an observational study examining timing and characteristics of fecal microbiota transplantation failures. Clin Gastroenterol Hepatol. 2018; 16:1832–1833.