Advancing Access to Intestinal Microbiota Transplant: Bridging the Gap Between National Practices and the European Strategy

Authors

  • Liliana Dinis Comprehensive Health Research Centre (CHRC). NOVA Medical School. Universidade NOVA de Lisboa. Lisbon. & YourBiome®. Évora. https://orcid.org/0000-0002-5069-2362
  • Hélder Pinheiro NOVA Medical School. Universidade NOVA de Lisboa. Lisbon. & Infectious Diseases Department. Hospital de Cascais Dr. José de Almeida. Cascais. https://orcid.org/0000-0001-6076-2670
  • Pedro Póvoa NOVA Medical School. Universidade NOVA de Lisboa. Lisbon. &Department of Critical Care Medicine. Hospital de São Francisco Xavier. Unidade Local de Saúde Lisboa Ocidental. Lisbon. https://orcid.org/0000-0002-7069-7304
  • Conceição Calhau Comprehensive Health Research Centre (CHRC). NOVA Medical School. Universidade NOVA de Lisboa. Lisbon. & Nutrition & Metabolism Department. CINTESIS@RISE. NOVA Medical School. Universidade NOVA de Lisboa. Lisbon. https://orcid.org/0000-0001-9567-3379
  • Diogo Pestana Comprehensive Health Research Centre (CHRC). NOVA Medical School. Universidade NOVA de Lisboa. Lisbon. & Nutrition & Metabolism Department. CINTESIS@RISE. NOVA Medical School. Universidade NOVA de Lisboa. Lisbon. https://orcid.org/0000-0001-6332-7914
  • Cláudia Marques Comprehensive Health Research Centre (CHRC). NOVA Medical School. Universidade NOVA de Lisboa. Lisbon. & Nutrition & Metabolism Department. CINTESIS@RISE. NOVA Medical School. Universidade NOVA de Lisboa. Lisbon. https://orcid.org/0000-0002-8365-7934

DOI:

https://doi.org/10.20344/amp.22750

Keywords:

Clostridioides difficile, Clostridium Infections, Europe, Fecal Microbiota Transplantation, Gastrointestinal Microbiome

Abstract

Clostridioides difficile is an opportunistic pathogen that can cause a range of conditions, from asymptomatic carriage to severe illness, posing a significant public health threat due to its high mortality rates and substantial healthcare costs. Traditional treatment options, including antibiotics, often fail to eradicate the infection, leading to recurrent cases that severely impact patients’ lives. Intestinal microbiota transplant (IMT) has emerged as an effective strategy for decolonizing pathogenic agents, demonstrating safety and efficacy, particularly in treating recurrent Clostridioides difficile infection (rCDI). Despite its potential, access to IMT is limited due to safety concerns, logistical challenges, and a lack of proper guidance, underscoring the urgent need for structured intestinal microbiota banks (IMBs). These organized facilities are crucial for the collection, screening, processing, and distribution of intestinal microbiota preparations, thereby facilitating the clinical application of IMT. In this narrative review, we discuss the relevance of applying IMT for the treatment of rCDI in Europe, with a focus on Portugal. We highlight the existence and distribution of IMBs across Europe and their importance in improving access to IMT. This review also addresses the challenges in creating an IMB and the development of such a structure in Portugal as a centralized repository for high-quality, standardized microbiota preparations, making IMT accessible for national hospitals. Additionally, it emphasizes the need to raise awareness among healthcare providers and the public to support the broader adoption of IMT.

Downloads

Download data is not yet available.

References

Khoruts A, Sadowsky MJ. Understanding the mechanisms of faecal microbiota transplantation. Nat Rev Gastroenterol Hepatol. 2016;13:508-16. DOI: https://doi.org/10.1038/nrgastro.2016.98

Marcella C, Cui B, Kelly CR, Ianiro G, Cammarota G, Zhang F. Systematic review: the global incidence of faecal microbiota transplantation-related adverse events from 2000 to 2020. Aliment Pharmacol Ther. 2021;53:33-42. DOI: https://doi.org/10.1111/apt.16148

Perler BK, Chen B, Phelps E, Allegretti JR, Fischer M, Ganapini V, et al. Long-term efficacy and safety of fecal microbiota transplantation for treatment of recurrent clostridioides difficile infection. J Clin Gastroenterol. 2020;54:701-6. DOI: https://doi.org/10.1097/MCG.0000000000001281

Malone DC, Armstrong EP, Gratie D, Pham SV, Amin A. A systematic review of real-world healthcare resource use and costs of clostridioides difficile infections. Antimicrob Steward Healthc Epidemiol. 2023;3:e17. DOI: https://doi.org/10.1017/ash.2022.369

Panchal P, Budree S, Scheeler A, Medina G, Seng M, Wong WF, et al. Scaling safe access to fecal microbiota transplantation: past, present, and future. Curr Gastroenterol Rep. 2018;20:14. DOI: https://doi.org/10.1007/s11894-018-0619-8

Finn E, Andersson FL, Madin-Warburton M. Burden of clostridioides difficile infection (CDI) - a systematic review of the epidemiology of primary and recurrent CDI. BMC Infect Dis. 2021;21:456. DOI: https://doi.org/10.1186/s12879-021-06147-y

Bakken JS, Borody T, Brandt LJ, Brill JV, Demarco DC, Franzos MA, et al. Treating clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol. 2011;9:1044-9. DOI: https://doi.org/10.1016/j.cgh.2011.08.014

Webb BJ, Subramanian A, Lopansri B, Goodman B, Jones PB, Ferraro J, et al. Antibiotic exposure and risk for hospital-associated clostridioides difficile infection. Antimicrob Agents Chemother. 2020;64:e02169-19. DOI: https://doi.org/10.1128/AAC.02169-19

Davies K, Lawrence J, Berry C, Davis G, Yu H, Cai B, et al. Risk factors for primary clostridium difficile infection; results from the observational study of risk factors for clostridium difficile infection in hospitalized patients with infective diarrhea (ORCHID). Front Public Health. 2020;8:293. DOI: https://doi.org/10.3389/fpubh.2020.00293

European Centre for Disease Prevention and Control. European surveillance of clostridioides (clostridium) difficile infections. Surveillance protocol version 2.4. Stockholm: ECDC; 2019.

Reigadas Ramírez E, Bouza ES. Economic burden of clostridium difficile infection in European countries. Adv Exp Med Biol. 2018;1050:1-12. DOI: https://doi.org/10.1007/978-3-319-72799-8_1

Jones AM, Kuijper EJ, Wilcox MH. Clostridium difficile: a European perspective. J Infect. 2013;66:115-28. DOI: https://doi.org/10.1016/j.jinf.2012.10.019

Wingen-Heimann SM, Davies K, Viprey VF, Davis G, Wilcox MH, Vehreschild MJ, et al. Clostridioides difficile infection (CDI): a pan-European multi-center cost and resource utilization study, results from the Combatting Bacterial Resistance in Europe CDI (COMBACTE-CDI). Clin Microbiol Infect. 2023;29:651.e1-651.e8. DOI: https://doi.org/10.1016/j.cmi.2022.12.019

van Prehn J, Reigadas E, Vogelzang EH, Bouza E, Hristea A, Guery B, et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect. 2021;27:S1-21. DOI: https://doi.org/10.1016/j.cmi.2021.09.038

Kelly CR, Yen EF, Grinspan AM, Kahn SA, Atreja A, Lewis JD, et al. Fecal microbiota transplantation is highly effective in real-world practice: initial results from the FMT national registry. Gastroenterol. 2021;160:183-92.e3. DOI: https://doi.org/10.1053/j.gastro.2020.09.038

Lee CH, Steiner T, Petrof EO, Smieja M, Roscoe D, Nematallah A, 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;315:142-9. DOI: https://doi.org/10.1001/jama.2015.18098

Ooijevaar RE, van Nood E, Goorhuis A, Terveer EM, van Prehn J, Verspaget HW, et al. Ten-year follow-up of patients treated with fecal microbiota transplantation for recurrent clostridioides difficile infection from a randomized controlled trial and review of the literature. Microorganisms. 2021;9:1-13. DOI: https://doi.org/10.3390/microorganisms9030548

Quraishi MN, Widlak M, Bhala N, Moore D, Price M, Sharma 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;46:479-93. DOI: https://doi.org/10.1111/apt.14201

Baunwall SM, Lee MM, Eriksen MK, Mullish BH, Marchesi JR, Dahlerup JF, et al. Faecal microbiota transplantation for recurrent clostridioides difficile infection: an updated systematic review and meta-analysis. EClinicalMedicine. 2020;29-30:100642. DOI: https://doi.org/10.1016/j.eclinm.2020.100642

Mamo Y, Woodworth MH, Wang T, Dhere T, Kraft CS. Durability and long-term clinical outcomes of fecal microbiota transplant treatment in patients with recurrent clostridium difficile infection. Clin Infect Dis. 2018;66:1705-11. DOI: https://doi.org/10.1093/cid/cix1097

Rokkas T, Gisbert JP, Gasbarrini A, Hold GL, Tilg H, Malfertheiner P, et al. A network meta-analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in recurrent clostridium difficile infection. United European Gastroenterol J. 2019;7:1051-63. DOI: https://doi.org/10.1177/2050640619854587

Weiss GA, Hennet T. Mechanisms and consequences of intestinal dysbiosis. Cell Mol Life Sci. 2017;74:2959-77. DOI: https://doi.org/10.1007/s00018-017-2509-x

Dehlholm-Lambertsen E, Hall BK, Jørgensen SM, Jørgensen CW, Jensen ME, Larsen S, et al. Cost savings following faecal microbiota transplantation for recurrent Clostridium difficile infection. Therap Adv Gastroenterol. 2019;12: 1756284819843002. DOI: https://doi.org/10.1177/1756284819843002

Birch CR, Paaske SE, Jensen MB, Baunwall SM, Ehlers LH, Hvas CL. Cost-effectiveness of faecal microbiota transplantation compared with vancomycin monotherapy for early clostridioides difficile infection: economic evaluation alongside a randomised controlled trial. J Hosp Infect. 2025;155:145-9. DOI: https://doi.org/10.1016/j.jhin.2024.11.003

Baunwall SM, Terveer EM, Dahlerup JF, Erikstrup C, Arkkila P, Vehreschild MJ, et al. The use of faecal microbiota transplantation (FMT) in Europe: a Europe-wide survey. Lancet Reg Health Eur. 2021;9:100181. DOI: https://doi.org/10.1016/j.lanepe.2021.100181

Nazareth C, Leitão I, Reis E, Inácio H, Martins F, Ramalheira E, et al. Epidemiology of clostridioides difficile infection in Portugal: a retrospective, observational study of hospitalized patients. Acta Med Port. 2022;35:270-8. DOI: https://doi.org/10.20344/amp.15890

Balsells E, Shi T, Leese C, Lyell I, Burrows J, Wiuff C, et al. Global burden of clostridium difficile infections: a systematic review and meta-analysis. J Glob Health. 2019;9:010407. DOI: https://doi.org/10.7189/jogh.09.010407

Gouveia C, Palos C, Pereira P, Roque Ramos L, Cravo M. Fecal microbiota transplant in a patient infected with multidrug-resistant bacteria: a case report. GE Port J Gastroenterol. 2020;28:56-61. DOI: https://doi.org/10.1159/000507263

Ponte A, Pinho R, Mota M, Silva J, Vieira N, Oliveira R, et al. Fecal microbiota transplantation in refractory or recurrent clostridium difficile infection: a real-life experience in a non-academic center. Rev Esp Enferm Dig. 2018;110:311-5. DOI: https://doi.org/10.17235/reed.2018.5099/2017

Silva JC, Ponte A, Mota M, Pinho R, Viera N, Oliveira R, et al. Fecal microbiota transplantation in the intestinal decolonization of carbapenamase-producing enterobacteriaceae. Rev Esp Enferm Dig. 2020;112:925-8. DOI: https://doi.org/10.17235/reed.2020.7150/2020

Liu Y, Alnababtah K, Cook S, Yu Y. Healthcare providers’ perception of faecal microbiota transplantation with clostridium difficile infection and inflammatory bowel disease: a quantitative systematic review. Therap Adv Gastroenterol. 2021;14:17562848211042679. DOI: https://doi.org/10.1177/17562848211042679

Green JE, Davis JA, Berk M, Hair C, Loughman A, Castle D, et al. Efficacy and safety of fecal microbiota transplantation for the treatment of diseases other than Clostridium difficile infection: a systematic review and meta-analysis. Gut Microbes. 2020;12:1-25. DOI: https://doi.org/10.1080/19490976.2020.1854640

Tkach S, Dorofeyev A, Kuzenko I, Boyko N, Falalyeyeva T, Boccuto L, et al. Current status and future therapeutic options for fecal microbiota transplantation. Medicina. 2022;58:84. DOI: https://doi.org/10.3390/medicina58010084

Wilkins LJ, Monga M, Miller AW. Defining dysbiosis for a cluster of chronic diseases. Sci Rep. 2019;9:1-10. DOI: https://doi.org/10.1038/s41598-019-49452-y

Dixit K, Chaudhari D, Dhotre D, Shouche Y, Saroj S. Restoration of dysbiotic human gut microbiome for homeostasis. Life Sci. 2021;278:119622. DOI: https://doi.org/10.1016/j.lfs.2021.119622

Mirsepasi-Lauridsen HC, Vrankx K, Engberg J, Friis-Møller A, Brynskov J, Nordgaard-Lassen I, et al. Disease-specific enteric microbiome dysbiosis in inflammatory bowel disease. Front Med. 2018;5:304. DOI: https://doi.org/10.3389/fmed.2018.00304

Wang L, Guo G, Xu Y, Li L, Yang B, Zhao D, et al. The effect of fecal microbiota transplantation on antibiotic-associated diarrhea and its impact on gut microbiota. BMC Microbiol. 2024;24:1-9. DOI: https://doi.org/10.1186/s12866-024-03261-0

Aron-Wisnewsky J, Clément K, Nieuwdorp M. Fecal microbiota transplantation: a future therapeutic option for obesity/diabetes? Curr Diab Rep. 2019;19:51. DOI: https://doi.org/10.1007/s11892-019-1180-z

Yang R, Chen Z, Cai J. Fecal microbiota transplantation: emerging applications in autoimmune diseases. J Autoimmun. 2023;141:103038. DOI: https://doi.org/10.1016/j.jaut.2023.103038

Sharma P, Agrawal A. Does modern research validate the ancient wisdom of gut flora and brain connection? A literature review of gut dysbiosis in neurological and neurosurgical disorders over the last decade. Neurosurg Rev. 2022;45:27-48. DOI: https://doi.org/10.1007/s10143-021-01516-2

Ortigao R, Pimentel-Nunes P, Dinis-Ribeiro M, Libanio D. Gastrointestinal microbiome - what we need to know in clinical practice. GE Port J Gastroenterol. 2020;27:336-51. DOI: https://doi.org/10.1159/000505036

Gupta S, Allen-Vercoe E, Petrof EO. Fecal microbiota transplantation: in perspective. Therap Adv Gastroenterol. 2016;9:229-39. DOI: https://doi.org/10.1177/1756283X15607414

Kho ZY, Lal SK. The human gut microbiome - a potential controller of wellness and disease. Front Microbiol. 2018;9:1835. DOI: https://doi.org/10.3389/fmicb.2018.01835

Cani PD. Human gut microbiome: hopes, threats and promises. Gut. 2018;67:1716-25. DOI: https://doi.org/10.1136/gutjnl-2018-316723

Kootte RS, Levin E, Salojärvi J, Smits LP, Hartstra AV, Udayappan SD, et al. Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metab. 2017;26:611-9.e6. DOI: https://doi.org/10.1016/j.cmet.2017.09.008

Moss EL, Falconer SB, Tkachenko E, Wang M, Systrom H, Mahabamunuge J, et al. Long-term taxonomic and functional divergence from donor bacterial strains following fecal microbiota transplantation in immunocompromised patients. PLoS One. 2017;12:1-16. DOI: https://doi.org/10.1101/109645

Serrano-Villar S, Talavera-Rodríguez A, Gosalbes MJ, Madrid N, Pérez-Molina JA, Elliott RJ, et al. Fecal microbiota transplantation in HIV: A pilot placebo-controlled study. Nat Commun. 2021;12:1139. DOI: https://doi.org/10.1038/s41467-021-21472-1

Sommer F, Anderson JM, Bharti R, Raes J, Rosenstiel P. The resilience of the intestinal microbiota influences health and disease. Nat Rev Microbiol. 2017;15:630-8. DOI: https://doi.org/10.1038/nrmicro.2017.58

Rothschild D, Weissbrod O, Barkan E, Kurilshikov A, Korem T, Zeevi D, et al. Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018;555:210-5. DOI: https://doi.org/10.1038/nature25973

de Groot P, Scheithauer T, Bakker GJ, Prodan A, Levin E, Khan MT, et al. Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time. Gut. 2019;69:502-12. DOI: https://doi.org/10.1136/gutjnl-2019-318320

Li SS, Zhu A, Benes V, Costea PI, Hercog R, Hildebrand F, et al. Durable coexistence of donor and recipient strains after fecal microbiota transplantation. Science. 2016;352:586-9. DOI: https://doi.org/10.1126/science.aad8852

Maida M, Mcilroy J, Ianiro G, Cammarota G. Faecal microbiota transplantation as emerging treatment in European countries. Adv Exp Med Biol. 2018;1050:177-95. DOI: https://doi.org/10.1007/978-3-319-72799-8_11

Jørgensen SM, Hvas CL, Dahlerup JF, Mikkelsen S, Ehlers L, Hammeken LH, et al. Banking feces: a new frontier for public blood banks? Transfusion. 2019;59:2776-82. DOI: https://doi.org/10.1111/trf.15422

Nicco C, Paule A, Konturek P, Edeas M. From donor to patient: collection, preparation and cryopreservation of fecal samples for fecal microbiota transplantation. Diseases. 2020;8:9. DOI: https://doi.org/10.3390/diseases8020009

Cammarota G, Ianiro G, Tilg H, Rajilić-Stojanović M, Kump P, Satokari R, et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017;66:569-80. DOI: https://doi.org/10.1136/gutjnl-2016-313017

Keller JJ, Ooijevaar RE, Hvas CL, Terveer EM, Lieberknecht SC, Högenauer C, et al. A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group. United European Gastroenterol J. 2021;9:229-47. DOI: https://doi.org/10.1177/2050640620967898

Cammarota G, Ianiro G, Kelly CR, Mullish BH, Allegretti JR, Kassam Z, et al. International consensus conference on stool banking for faecal microbiota transplantation in clinical practice. Gut. 2019;68:2111-21. DOI: https://doi.org/10.1136/gutjnl-2019-319548

Chen J, Zaman A, Ramakrishna B, Olesen SW. Stool banking for fecal microbiota transplantation: methods and operations at a large stool bank. Front Cell Infect Microbiol. 2021;11:622949. DOI: https://doi.org/10.3389/fcimb.2021.622949

Kragsnaes MS, Nilsson AC, Kjeldsen J, Holt HM, Rasmussen KF, Georgsen J, et al. How do I establish a stool bank for fecal microbiota transplantation within the blood- and tissue transplant service? Transfusion. 2020;60:1135-41. DOI: https://doi.org/10.1111/trf.15816

Terveer EM, van Beurden YH, Goorhuis A, Seegers JF, Bauer MP, van Nood E, et al. How to: establish and run a stool bank. Clin Microbiol Infect. 2017;23:924-30. DOI: https://doi.org/10.1016/j.cmi.2017.05.015

European Directorate for the Quality of Medicines & HealthCare. Guide to the quality and safety of tissues and cells for human application. 5th ed. Strasbourg: EDQM Council of Europe; 2022.

Rode AA, Bytzer P, Pedersen OB, Engberg J. Establishing a donor stool bank for faecal microbiota transplantation: methods and feasibility. Eur J Clin Microbiol. 2019;38:1837-47. DOI: https://doi.org/10.1007/s10096-019-03615-x

Nakov R, Lyutakov I, Mitkova A, Gerova V, Petkova V, Giragosyan S, et al. Establishment of the first stool bank in an Eastern European country and the first series of successful fecal microbiota transplantations in Bulgaria. Eur Rev Med Pharmacol Sci. 2021;25:390-6.

Ianiro G, Porcari S, Bibbò S, Giambò F, Quaranta G, Masucci L, et al. Donor program for fecal microbiota transplantation: a 3-year experience of a large-volume Italian stool bank. Dig Liver Dis. 2021;53:1428-32. DOI: https://doi.org/10.1016/j.dld.2021.04.009

Terveer EM, Vendrik KE, Ooijevaar RE, Lingen E van, Boeije-Koppenol E, Nood E van, et al. Faecal microbiota transplantation for clostridioides difficile infection: four years’ experience of the Netherlands Donor Feces Bank. United European Gastroenterol J. 2020;8:1236-47. DOI: https://doi.org/10.1177/2050640620957765

Kim KO, Schwartz MA, Lin OS, Chiorean MV, Gluck M. Reducing cost and complexity of fecal microbiota transplantation using universal donors for recurrent clostridium difficile Infection. Adv Ther. 2019;36:2052-61. DOI: https://doi.org/10.1007/s12325-019-00974-x

Ismael S, Silvestre MP, Vasques M, Araújo JR, Morais J, Duarte MI, et al. A pilot study on the metabolic impact of mediterranean diet in type 2 diabetes: is gut microbiota the key? Nutrients. 2021;13:1228.~ DOI: https://doi.org/10.3390/nu13041228

Silva R, Dinis L, Peris A, Novais L, Calhau C, Pestana D, et al. Fecal microbiota transplantation - could stool donors’ and receptors’ diet be the key to future success? Front Gastroenterol. 2023;2:1-6. DOI: https://doi.org/10.3389/fgstr.2023.1270899

Moreira-Rosário A, Marques C, Pinheiro H, Araújo JR, Ribeiro P, Rocha R, et al. Gut microbiota diversity and c-reactive protein are predictors of disease severity in COVID-19 patients. Front Microbiol. 2021;12:705020. DOI: https://doi.org/10.3389/fmicb.2021.705020

European Commission. Meeting of the competent authorities for tissues and cells summary report. 2015. [cited 2025 Aug 22]. Available from: https://health.ec.europa.eu/system/files/2016-11/ev_20141203_sr_en_0.pdf.

European Commission. Regulation of the European parliament and of the council on standards of quality and safety for substances of human origin intended for human application and repealing. 2022. [cited 2025 Aug 22]. Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:52022PC0338.

Kelly CR, Laine LA, Wu GD. Monitoring fecal microbiota transplantation practice in a rapidly evolving health and regulatory environment. Gastroenterology. 2020;159:2004-6. DOI: https://doi.org/10.1053/j.gastro.2020.08.039

Downloads

Published

2025-08-27

How to Cite

1.
Dinis L, Pinheiro H, Póvoa P, Calhau C, Pestana D, Marques C. Advancing Access to Intestinal Microbiota Transplant: Bridging the Gap Between National Practices and the European Strategy. Acta Med Port [Internet]. 2025 Aug. 27 [cited 2025 Dec. 7];38(10):639-47. Available from: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/22750

Issue

Section

Review Articles