Facilitar o Acesso ao Transplante de Microbiota Intestinal: Alinhar as Práticas Nacionais com a Estratégia Europeia
DOI:
https://doi.org/10.20344/amp.22750Palavras-chave:
Clostridioides difficile, Europa, Infecções por Clostridium, Microbioma Intestinal, Transplante de Microbiota FecalResumo
Clostridioides difficile é um agente patogénico oportunista capaz de causar desde condições assintomáticas até doenças clínicas graves, representando uma significativa ameaça à saúde pública devido às suas elevadas taxas de mortalidade e aos substanciais custos associados aos cuidados de saúde. Os tratamentos tradicionais, incluindo antibióticos, muitas vezes falham em erradicar a infeção, o que leva a recorrências que afetam de forma significativa a qualidade de vida dos pacientes. O transplante de microbiota intestinal (TMI) surgiu como uma estratégia eficaz para a descolonização de agentes patogénicos, demonstrando segurança e eficácia, especialmente no tratamento de infeções recorrentes por Clostridioides difficile. Apesar do seu grande potencial, o acesso ao TMI é limitado devido a questões de segurança, desafios logísticos e à ausência de diretrizes claras, o que destaca a necessidade urgente de bancos de microbiota intestinal (BMI). Estas estruturas são essenciais para a recolha, rastreio, processamento e distribuição das preparações de microbiota intestinal, facilitando, assim, a implementação clínica do TMI. Nesta revisão narrativa, discutimos a relevância da aplicação do TMI no tratamento de infeções recorrentes por C. difficile na Europa, com especial enfoque em Portugal. Destacamos a existência e distribuição dos BMI na Europa e a sua importância na melhoria do acesso ao TMI. Esta revisão aborda também os desafios da criação de um BMI em Portugal, destacando a importância de um repositório centralizado de preparações de microbiota padronizadas e de alta qualidade, tornando o TMI acessível aos hospitais nacionais. Adicionalmente, sublinha a necessidade de sensibilizar os profissionais de saúde e o público em geral para apoiar a adoção mais ampla do TMI.
Downloads
Referências
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
Publicado
Como Citar
Edição
Secção
Licença
Direitos de Autor (c) 2025 Acta Médica Portuguesa
Este trabalho encontra-se publicado com a Creative Commons Atribuição-NãoComercial 4.0.
Todos os artigos publicados na AMP são de acesso aberto e cumprem os requisitos das agências de financiamento ou instituições académicas. Relativamente à utilização por terceiros a AMP rege-se pelos termos da licença Creative Commons ‘Atribuição – Uso Não-Comercial – (CC-BY-NC)’.
É da responsabilidade do autor obter permissão para reproduzir figuras, tabelas, etc., de outras publicações. Após a aceitação de um artigo, os autores serão convidados a preencher uma “Declaração de Responsabilidade Autoral e Partilha de Direitos de Autor “(http://www.actamedicaportuguesa.com/info/AMP-NormasPublicacao.pdf) e a “Declaração de Potenciais Conflitos de Interesse” (http://www.icmje.org/conflicts-of-interest) do ICMJE. Será enviado um e-mail ao autor correspondente, confirmando a receção do manuscrito.
Após a publicação, os autores ficam autorizados a disponibilizar os seus artigos em repositórios das suas instituições de origem, desde que mencionem sempre onde foram publicados e de acordo com a licença Creative Commons
