Gut Microbiota and Fecal Microbiota Transplantation: Clinical Applications and Future Perspectives

Yıl 2025, Cilt: 34 Sayı: 1, 31 - 43, 31.03.2025

Eda Keskin

https://doi.org/10.17827/aktd.1589820

Öz

The intestinal microbiota is the most heavily colonized area of the human body and represents a complex ecosystem. It has been strongly suggested that the microbiota plays an important role in human health through various mechanisms. Evidence shows that the microbiota is effective in the host's defense against pathogens and can participate in the maturation of the innate immune system. Today, the microbiota has been associated with a wide variety of health problems, from metabolic diseases such as obesity, metabolic syndrome, and insulin resistance to neurological and intestinal disorders. As a result of studies proving this relationship between the microbiota and many diseases, fecal microbiota transplantation (FMT) has become a focus of research in biomedical and clinical medicine. This procedure involves transferring feces from a healthy donor, which is processed and then transplanted into the recipient's intestine. It has been approved as a standard treatment for recurrent Clostridium difficile infection in guidelines. In recent years, interest in the therapeutic potential of FMT for metabolic, autoimmune, and other diseases not previously thought to be associated with the microbiota has increased. Promising results have also been obtained in the treatment of inflammatory bowel diseases, irritable bowel syndrome, and metabolic diseases. The safety of FMT in pregnancy is based on limited case reports. According to systematic reviews and meta-analyses, the use of this new treatment, which has minimal side effects (such as abdominal pain, cramps, fever, nausea, vomiting, bloating and infection), has not yet been standardised. Therefore, it is important to establish a rigorous screening process and selection criteria for donors to ensure safe and effective transplantation. The transplantation protocol should be optimized and standardized for each specific indication. However, more clinical studies are needed to more clearly define this treatment strategy, the transplantation process, and the many potential future indications.

Anahtar Kelimeler

Clostridium difficile infection, fecal microbiota transplantation, gut microbiota, intestinal diseases, metabolic diseases

Bağırsak Mikrobiyotası ve Fekal Mikrobiyota Transplantasyonu: Klinik Uygulamalar ve Gelecek Perspektifleri

Öz

Bağırsak mikrobiyotası insan vücudunun en ağır kolonize bölgesi olup karmaşık bir ekosisteme sahiptir. Mikrobiyotanın insan sağlığında çeşitli mekanizmalarla önemli bir rol oynadığı şiddetle öne sürülmüştür. Kanıtlar, mikrobiyotanın konakçının patojenlere karşı savunmasında etkili olduğunu, doğal bağışıklık sisteminin olgunlaşmasına ve işlevine katılabildiğini göstermektedir. Günümüzde bağırsak mikrobiyotası başta bağırsak hastalıkları olmak üzere obezite, metabolik sendrom, insülin direnci gibi metabolik hastalıklardan nörolojik hastalıklara kadar çok çeşitli sağlık sorunları ile ilişkilendirilmiştir. Pek çok hastalık ile mikrobiyota arasındaki bu ilişkiyi kanıtlayan çalışmalar sonucunda, fekal mikrobiyota transplantasyonu (FMT) biyomedikal ve klinik tıpta araştırma odağı haline gelmiştir. FMT, sağlıklı bir donörden alınan dışkının, çeşitli süreçlerden geçirilerek hazırlandıktan sonra bir alıcı bağırsağına farklı yollarla aktarılmasından oluşan bir prosedürdür. Resmi kılavuzlarda tekrarlayan Clostridium difficile enfeksiyonu için standart bir tedavi olarak onaylanmıştır. Son yıllarda metabolik, otoimmün ve daha önce mikrobiyota ile ilişkili olduğu düşünülmeyen diğer hastalıklar için FMT’nin terapötik potansiyeline ilgi artmıştır. İnflamatuar bağırsak hastalıkları, irritabl bağırsak sendromu ve metabolik hastalıkların tedavisinde de umut verici sonuçlar elde edilmiştir. Gebelikte FMT’nin güvenliği ise sınırlı bir vaka raporuna dayanmaktadır. Yapılan sistematik çalışmalar ile meta analizlere dayanarak minimal yan etkileri (karın ağrısı, kramplar, ateş, bulantı, kusma, şişkinlik, enfeksiyon gibi) olan bu yeni tedavi yönteminin uygulama süreçleri henüz standartlaştırılmamıştır. Bu nedenle, transplantasyonun güvenli ve etkili bir şekilde uygulanabilmesi için donör seçiminde titiz bir tarama sürecinin ve standartların oluşturulması önemlidir. Transplantasyon protokolü her ayrı endikasyon için optimize edilmeli ve standartlaştırılmalıdır Bununla birlikte, transplantasyon süreci ve gelecekteki birçok potansiyel endikasyon için bu tedavi stratejisinin daha net belirlenmesi adına daha çok klinik çalışmalara ihtiyaç duyulmaktadır.

Anahtar Kelimeler

Bağırsak hastalıkları, bağırsak mikrobiyotası, Clostridium difficile enfeksiyonu, fekal mikrobiyota transplantasyonu, metabolik hastalıklar

Kaynakça

• 1. Murphy AB, Dinan TG, Cryan JF, Stanton C, Ross RP. Probiotics as curators of a healthy gut microbiota: Delivering the solution. In: The Gut-Brain Axis: Dietary, Probiotic, and Prebiotic Interventions on the Microbiota. 1st ed. (Eds Hyland N, Stanton C):65-88. UK, Academic Press, 2016.
• 2. Marques TM, Holster S, Wall R, König J, Brummer RJ, de Vos WM. Correlating the gut microbiome to health and disease. In: The Gut-Brain Axis: Dietary, Probiotic, and Prebiotic Interventions on the Microbiota. 1st ed. (Eds Hyland N, Stanton C):261-291. UK, Academic Press, 2016.
• 3. Zhang F, Cui B, He X, Nie Y, Wu K, Fan D; FMT-standardization Study Group. Microbiota transplantation: concept, methodology and strategy for its modernization. Protein Cell. 2018;9(5):462-473.
• 4. Meckel KR, Kiraly DD. A potential role for the gut microbiome in substance use disorders. Psychopharmacology (Berl). 2019;236(5):1513-1530.
• 5. Vemuri R, Gundamaraju R, Shastri MD, Shukla SD, Kalpurath K, Ball M, et al. Gut microbial changes, interactions, and their implications on human lifecycle: An ageing perspective. Biomed Res Int. 2018;2018:4178607.
• 6. Kim YS, Unno T, Kim BY, Park MS. Sex differences in gut microbiota. World J Mens Health. 2020;38(1):48-60.
• 7. Klement RJ, Pazienza V. Impact of different types of diet on gut microbiota profiles and cancer prevention and treatment. Medicana. 2019;55(4);84.
• 8. Lazar V, Ditu LM, Pircalabioru GG, Picu A, Petcu L, et al. Gut microbiota, host organism and diet trialogue in diabetes and obesity. Front Nutr. 2019;6;21.
• 9. Pickard JM, Zeng MY, Caruso R, Nunez G. Gut microbiota: Role in pathogen colonization, immune responses and inflammatory disease. Immunol Rev. 2017;279(1):70-89.
• 10. Ishiguro E, Haskey N, Campbell K. Gut Microbiota: Interactive effects on nutrition and health, p.17-39, Academic Press.UK, 2018.
• 11. Cheng HY, Ning MX, Chen DK, Ma WT. Interactions between the gut microbiota and the host innate immune response against pathogens. Front Immunol. 2019;10:607-618.
• 12. Wang B, Yao M, Lv L, Ling Z, Li L. The human microbiota in health and disease. Engineering. 2017;3(1):71-82.
• 13. König J, Brummer RJ. Modulation of the gut ecosystem irritable bowel syndrome. In: Pharmato-Nutrition: An Overview. 1st ed. (Eds Folkerts G, Garssen J):p.55-73. London, Aapspress-Springer, 2014.
• 14. Reygner J, Kapel N. Current status of fecal microbiota transplantation. In: Microbiome and Metabolome in Diagnosis, Therapy, and Other Strategic Applications. 1st ed. (Eds Faintuch J, Faintuch S.):155-165. UK, Academic Press, 2019.
• 15. Vindigni SM, Surawicz CM. Fecal Microbiota Transplantation. Gastroenterol Clin North Am. 2017;46(1):171-185.
• 16. Quraishi MN, Widlak M, Bhala N, Moore D, Price M, Sharma N, Iqbal TH. 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(5):479-493.
• 17. Wang S, Xu M, Wang W, Cao X, Piao M, et al. Systematic review: Advers events of fecal microbiota transplantation. PLoS One. 2016;11(8):e0161174.
• 18. Czepiel J, Dróżdż M, Pituch H, Kuijper EJ, Perucki W, Mielimonka A, et al. Clostridium difficile infection: review. Eur J Clin Microbiol Infect Dis. 2019;38(7):1211-1221.
• 19. U.S. Food and Drug Administration. FDA Guidance Document: Enforcement policy regarding investigational new drug requirements for use of fecal microbiota for transplantation to treat Clostridium difficile infection not responsive to standard therapies. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enforcement-policy-regarding-investigational-new-drug-requirements-use-fecal-microbiota.
• 20. Kelly CR, Kahn S, Kashyap P, Laine L, Rubin D, Atreja A, et al. Update on FMT 2015: Indications, methodologies, mechanisms and outlook. Gastroenterelogy. 2015;149(1):223-237.
• 21. 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(4):166-172,.
• 22. Greenberg SA, Youngster I, Cohen NA, Livovsky DM, Strahilevitz J, Israeli E. Five years of fecal microbiota transplantation – an update of the Israeli experience. World J Gastroenterol. 2018;24(47):5403-5414.
• 23. Krajicek E, Fischer M, Allegretti JR, Kelly CR. Nuts and bolts of fecal microbiota transplantation. 2019;17(2):345-352.
• 24. Paramsothy S, Borody TJ, Lin E, Finlayson S, Walsh AJ, Samuel D, et al. Donor recruitment for fecal microbiota transplantation. Inflamm Bowel Dis. 2015;21(7):1600-1606.
• 25. Turse EP, Dailey FE, Ghouri YA, Tahan V. Fecal microbiota transplantation donation: the gift that keeps on giving. Curr Opin Pharmacol. 2019;49:24.
• 26. Marotz CA, Zarrinpar A. Treating obesity and metabolic syndrome with fecal microbiota transplantation. Yale J Biol Med. 2016;89:383-388.
• 27. Wang JW, Kuo CH, Kuo FC, Wang YK, Hsu WH, Yu FJ, et al. Fecal microbiota transplantation: Review and update. J Formos Med Assoc. 2018;118 Suppl 1:23-31.
• 28. Kelly BJ, Tebas P. Clinical practice and infrastructure review of fecal microbiota transplantation for Clostridium difficile infection. Chest. 2018;153(1):266-277.
• 29. 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(1):18-29.
• 30. Cammarota G, Ianiro G, Tilg H, Rajilić-Stojanović M, Kump P, Satokari R; European FMT Working Group. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017;66(4):569-580.
• 31. Fine S, Kelly CR. FMT in Clostridium difficile and other potential uses. In: The Microbiota in Gastrointestinal Pathophysiology Implications for Human Health, Prebiotics, Probiotics, and Dysbiosis. 1st ed. (Eds Folch MH, Ringel Y, Walker WA):315-326. UK, Academic Press, 2017.
• 32. Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107(5):761-767.
• 33. Lee CH, Steiner T, Petrof EO, Smieja M, Roscoe D, Nematallah A. Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent Clostridium difficile infection. JAMA. 2016;315(2):142-149.
• 34. Barnes D, Park KT. Donor considerations in fecal microbiota transplantation. Curr Gastroenterol Rep. 2017;19:10-14.
• 35. Ramai D, Zakhia K, Ofosu A, Ofori E, Reddy M. Fecal microbiota transplantation: donor relation, fresh or frozen, delivery methods, cost-effectiveness. Ann Gastroenterol. 2019;32(1):30-38.
• 36. Bhutiani N, Schucht JE, Miller KR, McClave SA. Technical aspects of fecal microbial transplantation (FMT). Curr Gastroenterol Rep. 2018;20(7):30-36.
• 37. Furuya-Kanamori L, Doi SA, Paterson DL, Helms SK, Yakob L, McKenzie SJ, et al. Upper versus lower gastrointestinal delivery for transplantation of fecal microbiota in recurrent or refractory Clostridium difficile infection: A collaborative analysis of individual patient data from 14 studies. J Clin Gastroenterol. 2017;51(2):145-150.
• 38. Reigadas E, Olmedo M, Valerio M, Vázquez-Cuesta S, Alcalá L, et al. Fecal microbiota transplantation for recurrent Clostridium difficile infection: Experience, protocol, and results. Res Esp Quimioter. 2018;31(5):411-418.
• 39. 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(11):1832-33.
• 40. Choi HH, Cho YS. Fecal microbiota transplantation: current applications, effectiveness, and future perspectives. Clin Endosc. 2016;49(3):257-265.
• 41. Dailey FE, Turse EP, Daglilar E, Tahan V. The dirty aspects of fecal microbiota transplantation: a review of its adverse effects and complications. Curr Opin Pharmacol. 2019;49:29-33.
• 42. DeFilipp Z, Bloom PP, Torres Soto M, Mansour MK, Sater MRA, Huntley MH, et al. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant. N Engl J Med. 2019;381:2043–2050.
• 43. Vaughn BP, Rank KM, Khoruts A. Fecal microbiota transplantation: Current status in treatment of GI and liver disease. Clin Gastroenterol Hepatol. 2019;17(2):353-361.
• 44. Abu-Sbeih H, Ali FS, Wang Y. Clinical review on the utility of fecal microbiota transplantation in immunocompromised patients. Curr Gastroenterol Rep. 2019;21(4):8.
• 45. Alrabaa S, Jariwala R, Zeitler K, Montero J. Fecal microbiota transplantation outcomes in immunocompetent and immunocompromised patients: A single-center experience. Transpl Infect Dis. 2017;19(4):10.1111/tid.12726.
• 46. Saeedi BJ, Morison DG, Kraft CS, Dhere T. Fecal microbiota transplant for Clostridium difficile infection in a pregnant patient. Obstet Gynecol. 2017;129:507–509.
• 47. Crowley E, Muise A. Inflammatory bowel disease: What very early onset disease teaches us. Gastroenterol Clin North Am. 2018;47(4):755-772.
• 48. Sairenji T, Collins KL, Evans DV. An Update on inflammatory bowel disease. Prim Care. 2017;44(4):673-692.
• 49. Syal G, Kashani A, Shih DQ. Fecal microbiota transplantation in inflammatory bowel disease-a primer for the internists. Am J Med. 2018;131(9):1017-24.
• 50. Fischer M, Kao D, Kelly C, Kuchipudi A, Jafri SM, Blumenkehl M, et al. Fecal microbiota transplantation is safe and efficacious for recurrent or refractory Clostridium difficile infection in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2016;22(10):2402-2409.
• 51. Paramsothy S, Paramsothy R, Rubin DT, Kamm MA, Kaakoush NO, et al. Faecal microbiota transplantation for inflammatory bowel disease: A systematic review and meta-analysis. J Crohns Colitis. 2017;11(10):1180-1199.
• 52. Alammar N, Stein E. Irritable bowel syndrome what treatments really work. Med Clin North Am. 2019;103(1):137-152.
• 53. Farmer AD, Ruffle JK. Irritable bowel syndrome. Medicine. 2015;8(3):265-278.
• 54. Defrees DN, Bailey J. Irritable bowel syndrome epidemiology, pathophysiology, diagnosis, and treatment. Prim Care. 2017;44(4):655-671.
• 55. Principi N, Cozzali R, Farinelli E, Brusaferro A, Esposito S. Gut dysbiosis and irritable bowel syndrome: the potential role of probiotics. J Infect. 2018;76(2):111-120.
• 56. Johnsen PH, Hilpüsch F, Cavanagh JP, Leikanger IS, Kolstad C, Valle PC, 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 Gastroentererol Hepatol. 2018;3(1):17-24.
• 57. Manges AR, Steiner TS, Wright AJ. Fecal microbiota transplantation for the intestinal decolonization of extensively antimicrobialresistant opportunistic pathogens: a review. Infect Dis (Lond). 2016;48(8):587-592.
• 58. Ooijevaar RE, Terveer EM, Verspaget HW, Kuijper EJ, Keller JJ. Clinical application and potential of fecal microbiota transplantation. Annu Rev Med. 2019;70:335-351.
• 59. Saha S, Tariq R, Tosh PK, Khanna S. Faecal Microbiota transplantation for eradicating carriage of multidrug-resistant organisms: a systematic review. Clin Microbiol Infect. 2019;25(8):958-963.
• 60. Tavoukjian V. Faecal microbiota transplantation for the decolonisation of antibiotic-resistant bacteria in the gut: a systematic review and meta-analysis. J Hosp Infect. 2019;102(2):174-188.
• 61. Khanna S. Microbiota replacement therapies: Innovation in gastrointestinal care. Clin Pharmacol Ther. 2018;103(1):102-111.
• 62. 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(4):611-619.
• 63. Di Luccia B, Crescenzo R, Mazzoli A, Cigliano L, Venditti P, Walser JC, et al. Rescue of fructose-induced metabolic syndrome by antibiotics or faecal transplantation in a rat model of obesity. PLoS One. 2015;10(8):e0134893.
• 64. Sun W, Guo Y, Zhang S, Chen Z, Wu K, Liu Q, et al. Fecal microbiota transplantation can alleviate gastrointestinal transit in rats with high-fat diet-induced obesity via regulation of serotonin biosynthesis. Biomed Res Int. 2018;2018:8308671.
• 65. Zhou D, Pan Q, Shen F, Cao HX, Ding WJ, Chen YW, et al. Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota. Sci Rep. 2017;7(1):1529.
• 66. Groot PF, Frissen MN, de Clercq, Nieuwdorp M. Fecal microbiota transplantation in metabolic syndrome: history, present and future. Gut Microbes. 2017;8(3):253-267.