Faecal Microbiota Transplantation as Emerging Treatment in European Countries

  • Marcello Maida
  • James Mcilroy
  • Gianluca Ianiro
  • Giovanni Cammarota
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1050)


Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections in the world and is a leading cause of morbidity and mortality in hospitalized patients.

Although several antibiotics effectively treat CDI, some individuals do not respond to these drugs and may be cured by transplanting stool from healthy donors. This procedure, termed Faecal Microbiota Transplantation (FMT), has demonstrated remarkable efficacy as a treatment for recurrent CDI.

FMT has also been investigated in other diseases and disorders where perturbations to the gut microbiota have been theorized to play a causative role in pathogenesis and severity, such as inflammatory bowel disease (IBD). Although FMT is currently not recommended to cure IBD patients in clinical practice, several studies have recently been carried out with promising results. The aim of future research is therefore to standardize protocols and develop FMT as a therapeutic option for these patients.

This review summarizes data on the use of FMT as a treatment for CDI and IBD, with special attention given to studies conducted in European countries.


Clostridium difficile European Faecal microbiota transplantation Fecal Inflammatory bowel disease 


Conflict-of-Interest Statement

James McIlroy has received personal fees from EnteroBiotix during the conduct of this manuscript.


  1. Anderson JL, Edney RJ, Whelan K (2012) Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease. Aliment Pharmacol Ther 36:503–516CrossRefGoogle Scholar
  2. Angelberger S, Reinisch W, Makristathis A et al (2013) Temporal bacterial community dynamics vary among ulcerative colitis patients after fecal microbiota transplantation. Am J Gastroenterol 108:1620–1630CrossRefGoogle Scholar
  3. Asha NJ, Tompkins D, Wilcox MH (2006) Comparative analysis of prevalence, risk factors, and molecular epidemiology of antibiotic-associated diarrhea due to Clostridium difficile, Clostridium perfringens, and Staphylococcus aureus. J Clin Microbiol 44:2785–2791CrossRefGoogle Scholar
  4. Bafeta A, Yavchitz A, Riveros C et al (2017) Methods and reporting studies assessing fecal microbiota transplantation: a systematic review. Ann Intern Med 167:34–39CrossRefGoogle Scholar
  5. Bagdasarian N, Rao K, Malani PN (2015) Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA 313:398–408Google Scholar
  6. Bak S, Choi H, Lee J (2017) Fecal microbiota transplantation for refractory Crohn’s disease. Intest Res 15:244–248CrossRefGoogle Scholar
  7. Barbut F, Mastrantonio P, Delmée M et al (2007) Prospective study of Clostridium difficile infections in Europe with phenotypic and genotypic characterisation of the isolates. Clin Microbiol Infect 13:1048–1057Google Scholar
  8. Bassler D, Briel M, Montori VM et al (2010) Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis. JAMA 303:1180–1187CrossRefGoogle Scholar
  9. Bauer MP, Notermans DW, van Benthem BH et al (2011) Clostridium difficile infection in Europe: a hospital-based survey. Lancet 377:63–73Google Scholar
  10. Bennet JD, Brinkman M (1989) Treatment of ulcerative colitis by implantation of normal colonic flora. Lancet 1:164CrossRefGoogle Scholar
  11. Borody TJ, George L, Andrews P et al (1989) Bowel-flora alteration: a potential cure for inflammatory bowel disease and irritable bowel syndrome? Med J Aust 150:604PubMedGoogle Scholar
  12. Borody TJ, Leis S, McGrath K (2001) Treatment of chronic constipation and colitis using human probiotic infusions, Probiotics, prebiotics and new foods conference. Universita Urbaniana, RomeGoogle Scholar
  13. Borody TJ, Warren EF, Leis S et al (2003) Treatment of ulcerative colitis using fecal bacteriotherapy. J Clin Gastroenterol 37:42–47CrossRefGoogle Scholar
  14. Borody TJ, Campbell J, Torres M et al (2011a) Reversal of idiopathic thrombocytopenic purpura [ITP] with fecal microbiota transplantation [FMT]. Am J Gastroenterol 106:S352Google Scholar
  15. Borody TJ, Torres M, Campbell J et al (2011b) Reversal of inflammatory bowel disease (IBD) with recurrent faecal microbiota transplants (FMT). Am J Gastroenterol 106:S366–S366Google Scholar
  16. Borren NZ, Ghadermarzi S, Hutfless S et al (2017) The emergence of Clostridium difficile infection in Asia: a systematic review and meta-analysis of incidence and impact. PLoS One 12:e0176797Google Scholar
  17. Brandt LJ, Aroniadis OC, Mellow M et al (2012) Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol 107:1079–1087Google Scholar
  18. Cammarota G, Ianiro G, Cianci R et al (2015a) The involvement of gut microbiota in inflammatory bowel disease pathogenesis: potential for therapy. Pharmacol Ther 149:191–212CrossRefGoogle Scholar
  19. Cammarota G, Ianiro G, Magalini S et al (2015b) Decrease in surgery for Clostridium difficile infection after starting a program to transplant fecal microbiota. Ann Intern Med 163:487–488Google Scholar
  20. Cammarota G, Masucci L, Ianiro G et al (2015c) Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther 41:835–843Google Scholar
  21. Cammarota G, Ianiro G, Tilg H et al (2017) European consensus conference on faecal microbiota transplantation in clinical practice. Gut 66:569–580CrossRefGoogle Scholar
  22. Chu ND, Smith MB, Perrotta AR et al (2017) Profiling living bacteria informs preparation of fecal microbiota transplantations. PLoS One 12:e0170922CrossRefGoogle Scholar
  23. Cohen SH, Gerding DN, Johnson S, Society for Healthcare Epidemiology of America, Infectious Diseases Society of America et al (2010) Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol 31:431–455CrossRefGoogle Scholar
  24. Colman RJ, Rubin DT (2014) Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis 8:1569–1581CrossRefGoogle Scholar
  25. Costello SP, Conlon MA, Vuaran MS et al (2015) Faecal microbiota transplant for recurrent Clostridium difficile infection using long-term frozen stool is effective: clinical efficacy and bacterial viability data. Aliment Pharmacol Ther 42:1011–1018Google Scholar
  26. Costello SP, Soo W, Bryant RV et al (2017a) Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis. Aliment Pharmacol Ther 46:213–224CrossRefGoogle Scholar
  27. Costello S, Waters O, Bryant R et al (2017b) Short duration, low intensity pooled faecal microbiota transplantation induces remission in patients with mild-moderately active ulcerative colitis: a randomised controlled trial. J Crohns Colitis 11(suppl 1):S23CrossRefGoogle Scholar
  28. Cui B, Feng Q, Wang H et al (2015a) Fecal microbiota transplantation through mid-gut for refractory Crohn’s disease: safety, feasibility, and efficacy trial results. J Gastroenterol Hepatol 30:51–58CrossRefGoogle Scholar
  29. Cui B, Li P, Xu L et al (2015b) Step-up fecal microbiota transplantation strategy: a pilot study for steroid-dependent ulcerative colitis. J Transl Med 13:298CrossRefGoogle Scholar
  30. Debast SB, Bauer MP, Kuijper EJ et al (2014) European society of clinical microbiology and infectious diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect 20(Suppl 2):1–26Google Scholar
  31. Dutta SK, Girotra M, Garg S et al (2014) Efficacy of combined jejunal and colonic fecal microbiota transplantation for recurrent Clostridium difficile infection. Clin Gastroenterol Hepatol 12:1572–1576Google Scholar
  32. European Surveillance of Clostridium difficile infections. Surveillance protocol version 2.2. European Centre for Disease Prevention and Control. Stockholm: ECDC (2015) Latest Access July 2017
  33. Fang S, Kraft CS, Dhere T et al (2016) Successful treatment of chronic pouchitis utilizing fecal microbiota transplantation [FMT]: a case report. Int J Color Dis 31:1093–1094CrossRefGoogle Scholar
  34. Garborg K, Waagsbø B, Stallemo A et al (2010) Results of faecal donor instillation therapy for recurrent Clostridium difficile-associated diarrhoea. Scand J Infect Dis 42:857–861Google Scholar
  35. Gordon H, Harbord M (2014) A patient with severe Crohn’s colitis responds to faecal microbiota transplantation. J Crohns Colitis 8:256–257CrossRefGoogle Scholar
  36. Goyal A, Chu A, Calabro K et al (2016) Safety and efficacy of fecal microbiota transplant in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 63:S212Google Scholar
  37. Grewal CS, Sood A, Mehta V et al (2016) Role of fecal microbiota transplantation in patients with steroid dependent ulcerative colitis. Am J Gastroenterol 111:S1252–S1253CrossRefGoogle Scholar
  38. Hagel S, Fischer A, Ehlermann P et al (2016) Fecal microbiota transplant in patients with recurrent Clostridium difficile infection. Dtsch Arztebl Int 113(35–36):583–589Google Scholar
  39. Hamilton MJ, Weingarden AR, Sadowsky MJ et al (2012) Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol 107:761–767Google Scholar
  40. Hirsch BE, Saraiya N, Poeth K et al (2015) Effectiveness of fecal-derived microbiota transfer using orally administered capsules for recurrent Clostridium difficile infection. BMC Infect Dis 15:191Google Scholar
  41. Hota SS, Sales V, Tomlinson G et al (2017) Oral vancomycin followed by fecal transplantation versus tapering oral vancomycin treatment for recurrent Clostridium difficile infection: an open-label, randomized controlled trial. Clin Infect Dis 64:265–271Google Scholar
  42. Ianiro G, Bibbò S, Scaldaferri F et al (2014) Fecal microbiota transplantation in inflammatory bowel disease: beyond the excitement. Medicine (Baltimore) 93(19):e97CrossRefGoogle Scholar
  43. Ianiro G, Valerio L, Masucci L et al (2017) Predictors of failure after single faecal microbiota transplantation in patients with recurrent Clostridium difficile infection: results from a 3-year, single-centre cohort study. Clin Microbiol Infect 23:337.e1–337.e3Google Scholar
  44. Ishikawa D, Sasaki T, Osada T et al (2017) Changes in intestinal microbiota following combination therapy with fecal microbial transplantation and antibiotics for ulcerative colitis. Inflamm Bowel Dis 23:116–125CrossRefGoogle Scholar
  45. Jacob V, Crawford C, Cohen-Mekelburg S et al (2016) Fecal microbiota transplantation via colonoscopy is safe and effective in active ulcerative colitis. In: Advances in inflammatory bowel diseases. December 8–10, 2016. OrlandoGoogle Scholar
  46. Jorup-Ronstrom C, Hakanson A, Sandell S et al (2012) Fecal transplant against relapsing Clostridium difficile-associated diarrhea in 32 patients. Scand J Gastroenterol 47:548–552Google Scholar
  47. Kahn SA, Goeppinger SR, Vaughn BP et al (2014) Tolerability of colonoscopic fecal microbiota transplantation in IBD. Gastroenterology 146:S-581CrossRefGoogle Scholar
  48. Kao D, Hotte N, Gillevet P et al (2014) Fecal microbiota transplantation inducing remission in Crohn’s colitis and the associated changes in fecal microbial profile. J Clin Gastroenterol 48:625–628CrossRefGoogle Scholar
  49. Karakan T, Ibis M, Cindoruk Z et al (2016) Faecal microbiota transplantation as a rescue therapy for steroid-dependent and/or non-responsive patients with ulcerative colitis: a pilot study. In: 11th congress of the European Crohn’s and colitis organisation. March 16–19, 2016. AmsterdamGoogle Scholar
  50. Kassam Z, Hundal R, Marshall JK et al (2012) Fecal transplant via retention enema for refractory or recurrent Clostridium difficile infection. Arch Intern Med 172:191–193Google Scholar
  51. Kelly CR, Ihunnah C, Fischer M et al (2014) Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol 109:1065–1071Google Scholar
  52. Khan MA, Sofi AA, Ahmad U et al (2014) Efficacy and safety of, and patient satisfaction with, colonoscopic-administered fecal microbiota transplantation in relapsing and refractory community- and hospital-acquired Clostridium difficile infection. Can J Gastroenterol Hepatol 28:434–438Google Scholar
  53. Kump PK, Grochenig HP, Lackner S et al (2013) Alteration of intestinal dysbiosis by fecal microbiota transplantation does not induce remission in patients with chronic active ulcerative colitis. Inflamm Bowel Dis 19:2155–2165CrossRefGoogle Scholar
  54. Kump PK, Wurm P, Gröchenig HP et al (2015) Impact of antibiotic treatment before faecal microbiota transplantation [FMT] in chronic active ulcerative colitis. United European Gastroenterol J 3(5Suppl):A437Google Scholar
  55. Kunde S, Pham A, Bonczyk S et al (2013) Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis. J Pediatr Gastroenterol Nutr 56:597–601CrossRefGoogle Scholar
  56. Landy J, Walker AW, Li JV et al (2015) Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis. Sci Rep 5:12955CrossRefGoogle Scholar
  57. Lee CH, Belanger JE, Kassam Z et al (2014) The outcome and long-term follow-up of 94 patients with recurrent and refractory Clostridium difficile infection using single to multiple fecal microbiota transplantation via retention enema. Eur J Clin Microbiol Infect Dis 33:1425–1428Google Scholar
  58. Lee CH, Steiner T, Petrof EO et al (2016) Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent Clostridium difficile infection: a randomized clinical trial. JAMA 315:142–149Google Scholar
  59. Lessa FC, Mu Y, Bamberg WM et al (2015) Burden of Clostridium difficile infection in the United States. N Engl J Med 372:825–834Google Scholar
  60. Li YT, Cai HF, Wang ZH et al (2016) Systematic review with meta-analysis: long-term outcomes of faecal microbiota transplantation for Clostridium difficile infection. Aliment Pharmacol Ther 43:445–457Google Scholar
  61. Ma GK, Brensinger CM, Wu Q et al (2017) Increasing incidence of multiply recurrent Clostridium difficile infection in the United States: a cohort study. Ann Intern Med 167:152–158.
  62. MacConnachie AA, Fox R, Kennedy DR et al (2009) Faecal transplant for recurrent Clostridium difficile-associated diarrhoea: a UK case series. QJM 102:781–784Google Scholar
  63. Mandalia A, Ward A, Tauxe W et al (2016) Fecal transplant is as effective and safe in immunocompromised as non-immunocompromised patients for Clostridium difficile. Int J Color Dis 31:1059–1060Google Scholar
  64. Mattila E, Uusitalo-Seppala R, Wuorela M et al (2012) Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection. Gastroenterology 142:490–496Google Scholar
  65. McDonald LC, Killgore GE, Thompson A et al (2005) An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 353:2433–2441Google Scholar
  66. Meighani A, Hart BR, Mittal C et al (2016) Predictors of fecal transplant failure. Eur J Gastroenterol Hepatol 28:826–830Google Scholar
  67. Millan B, Park H, Hotte N et al (2016) Fecal microbial transplants reduce antibiotic-resistant genes in patients with recurrent Clostridium difficile infection. Clin Infect Dis 62:1479–1486Google Scholar
  68. Moayyedi P, Surette MG, Kim PT et al (2015) Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 149:102–109CrossRefGoogle Scholar
  69. Mullane KM, Cornely OA, Crook DW et al (2013) Renal impairment and clinical outcomes of Clostridium difficile infection in two randomized trials. Am J Nephrol 38:1–11CrossRefGoogle Scholar
  70. Nishida A, Imaeda H, Ohno M et al (2017) Efficacy and safety of single fecal microbiota transplantation for Japanese patients with mild to moderately active ulcerative colitis. J Gastroenterol 52:476–482CrossRefGoogle Scholar
  71. Paramsothy S, Kamm MA, Kaakoush NO et al (2017a) Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet 389:1218–1228CrossRefGoogle Scholar
  72. Paramsothy S, Paramsothy R, Rubin DT et al (2017b) Faecal microbiota transplantation for inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis 11:1180–1199. CrossRefPubMedGoogle Scholar
  73. Polak P, Freibergerova M, Jurankova J et al (2011) First experiences with faecal bacteriotherapy in the treatment of relapsing pseudomembranous colitis due to Clostridium difficile. Klin Mikrobiol Infekc Lek 17:214–217Google Scholar
  74. Rossen NG, Fuentes S, van der Spek et al (2015) Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology 149:110–118CrossRefGoogle Scholar
  75. Satokari R, Mattila E, Kainulainen V et al (2015) Simple faecal preparation and efficacy of frozen inoculum in faecal microbiota transplantation for recurrent Clostridium difficile infection—an observational cohort study. Aliment Pharmacol Ther 41:46–53CrossRefGoogle Scholar
  76. Scaldaferri F, Pecere S, Bruno G et al (2015) An open-label, pilot study to assess feasibility and safety of fecal microbiota transplantation in patients with mild-moderate ulcerative colitis: preliminary results. J Crohns Colitis 9:S278Google Scholar
  77. Schmid M, Frick JS, Malek N et al (2017) Successful treatment of pouchitis with Vedolizumab, but not fecal microbiota transfer (FMT), after proctocolectomy in ulcerative colitis. Int J Color Dis 32:597–598CrossRefGoogle Scholar
  78. Sokol H, Pigneur B, Watterlot L et al (2008) Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A 105:16731–16736Google Scholar
  79. Staley C, Hamilton MJ, Vaughn BP et al (2017) Successful resolution of recurrent Clostridium difficile infection using freeze-dried, encapsulated fecal microbiota; pragmatic cohort study. Am J Gastroenterol 112:940–947Google Scholar
  80. Stallmach A, Lange K, Buening J et al (2016) Fecal microbiota transfer in patients with chronic antibioticrefractory pouchitis. Am J Gastroenterol 111:441–443Google Scholar
  81. Stevens V, Dumyati G, Fine LS et al (2011) Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis 53:42–48CrossRefGoogle Scholar
  82. Surawicz CM, Brandt LJ, Binion DG et al (2013) Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 108:478–498Google Scholar
  83. Suskind DL, Brittnacher MJ, Wahbeh G et al (2015) Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active Crohn’s disease. Inflamm Bowel Dis 21:556–563CrossRefGoogle Scholar
  84. Swaminath A (2014) The power of poop: patients getting ahead of their doctors using self-administered fecal transplants. Am J Gastroenterol 109:777–778CrossRefGoogle Scholar
  85. Tang G, Yin W, Liu W (2017) Is frozen fecal microbiota transplantation as effective as fresh fecal microbiota transplantation in patients with recurrent or refractory Clostridium difficile infection: a meta-analysis? Diagn Microbiol Infect Dis 88:322–329Google Scholar
  86. Tauxe WM, Haydek JP, Rebolledo PA et al (2016) Fecal microbiota transplant for Clostridium difficile infection in older adults. Ther Adv Gastroenterol 9:273–281Google Scholar
  87. van Nood E, Vrieze A, Nieuwdorp M et al (2013) Duodenal infusion of donor faeces for recurrent Clostridium difficile. N Engl J Med 368:407–415Google Scholar
  88. Vaughn BP, Vatanen T, Allegretti JR et al (2016) Increased intestinal microbial diversity following fecal microbiota transplant for active Crohn’s disease. Inflamm Bowel Dis 22:2182–2190CrossRefGoogle Scholar
  89. Vermeire S, Joossens M, Verbeke K et al (2016) Donor species richness determines faecal microbiota transplantation success in inflammatory bowel disease. J Crohns Colitis 10:387–394CrossRefGoogle Scholar
  90. Warny M, Pepin J, Fang A et al (2005) Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 366:1079–1084Google Scholar
  91. Wei Y, Zhu W, Gong J et al (2015) Fecal microbiota transplantation improves the quality of life in patients with inflammatory bowel disease. Gastroenterol Res Pract 2015:517597CrossRefGoogle Scholar
  92. Wei Y, Gong J, Zhu W et al (2016) Pectin enhances the effect of fecal microbiota transplantation in ulcerative colitis by delaying the loss of diversity of gut flora. BMC Microbiol 16:1–9CrossRefGoogle Scholar
  93. Youngster I, Russell GH, Pindar C et al (2014a) Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA 312:1772–1778CrossRefGoogle Scholar
  94. Youngster I, Sauk J, Pindar C et al (2014b) 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 58:1515–1522Google Scholar
  95. Youngster I, Mahabamunuge J, Systrom HK et al (2016) Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection. BMC Med 14:134Google Scholar
  96. Zainah H, Hassan M, Shiekh-Sroujieh L et al (2014) Intestinal microbiota transplantation, a simple and effective treatment for severe and refractory Clostridium difficile infection. Dig Dis Sci 60:181–185Google Scholar
  97. Zhang T, Cui B, Li P et al (2016) Short-term surveillance of cytokines and C-reactive protein cannot predict efficacy of fecal microbiota transplantation for ulcerative colitis. PLoS One 11:e0158227CrossRefGoogle Scholar
  98. Zimlichman E, Henderson D, Tamir O et al (2013) Health care-associated infections. JAMA Intern Med 173:2039–2046CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Marcello Maida
    • 1
  • James Mcilroy
    • 2
  • Gianluca Ianiro
    • 3
  • Giovanni Cammarota
    • 3
  1. 1.Section of GastroenterologyS.Elia – Raimondi HospitalCaltanissettaItaly
  2. 2.School of Medicine, Medical Sciences and NutritionUniversity of AberdeenAberdeenUK
  3. 3.Gastroenterological AreaFondazione Policlinico Universitario Gemelli, Università Cattolica del Sacro CuoreRomeItaly

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