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FMT, applications and scientific evidence

Fecal Microbiota Transplantation

Fecal microbiota transplantation consists of the transfer of feces from a healthy donor into the gastrointestinal tract of a patient with a specific disease, associated with changes in microbiota (dysbiosis). The goal is to treat the associated condition by restoring a healthy gut microbiota.

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Given the vast scientific evidence, this treatment is currently recommended for the treatment of recurrent infection of Clostridioides difficile by the "European Society for Microbiology and Infectious Disease" and the "American College of Gastroenterology"

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Scientific evidence on the benefits of FMT is constantly growing and applications are being considered for several GI, metabolic, oncological and neurological diseases, among others.

Fecal Microbiota and C. difficile transplantation.

FMT is a life-saving treatment that is highly relevant given the increased prevalence, severity and mortality associated with recurrent C. difficile infection. Its high efficiency also allows to relieve the pressure and the economic cost on health systems.

 

Here are some of the clinical trials that have shown the FMT effectiveness in the treatment of antibiotic-resistant CDIs, or compared the effectiveness of FMT to conventional antibiotic therapy:

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  1. Hvas, C., Dahl Jørgensen, S., Jørgensen, S., Storgaard, M., Lemming, L., & Hansen, M. et al. (2019). Fecal Microbiota Transplantation Is Superior to Fidaxomicin for Treatment of Recurrent Clostridium difficile Infection. Gastroenterology, 156 (5), 1324-1332.e3. doi: 10.1053 / j.gastro.2018.12.019

  2. Friedman-Korn T, Livovsky DM, Maharshak N, Aviv Cohen N, Paz K, Bar-Gil Shitrit A, Goldin E, Koslowsky B. Fecal Transplantation for Treatment of Clostridium Difficile Infection in Elderly and Debilitated Patients. Dig Dis Sci. 2018 Jan; 63 (1): 198-203. doi: 10.1007 / s10620-017-4833-2. Epub 2017 Nov 13. PMID: 29134299.

  3. Webb BJ, Brunner A, Ford CD, Gazdik MA, Petersen FB, Hoda D. Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2016 Aug; 18 (4): 628-33. doi: 10.1111 / tid.12550

  4. 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. doi: 10.7326 / M16-0271

  5. Cammarota G, Masucci L, Ianiro G, et al. Randomized clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015. doi: 10.1111 / apt.13144

  6. van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. N Engl J Med. 2013. doi: 10.1056 / NEJMoa1205037

What is the best route of administration

The first fecal microbiota transplants were carried out via colonoscopy. Several clinical trials have been reporting high success rates either by administration by colonoscopy, by tube (nasogastric, nasoduodenal or nasojejunal) and oral administration in capsules:

 

 

  1. Kao D, Roach B, Silva M, et al. Effect of Oral Capsule – vs Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection . JAMA. 2017. doi: 10.1001 / jama.2017.17077

  2. Allegretti JR, Fischer M, Papa E, et al. Su1738 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): S540. doi: 10.1016 / S0016-5085 (16) 31855-8

  3. Youngster I, Mahabamunuge J, Systrom HK, et al. Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection. BMC Med. 2016. doi: 10.1186 / s12916-016-0680-9

  4. Hirsch BE, Saraiya N, Poeth K, Schwartz RM, Epstein ME, Honig G. Effectiveness of fecal-derived microbiota transfer using orally administered capsules for recurrent Clostridium difficile infection. BMC Infect Dis. 2015. doi: 10.1186 / s12879-015-0930-z

  5. 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 (11): 1515-1522. doi: 10.1093 / cid / ciu135

  6. 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 (17): 1772. doi: 10.1001 / jama.2014.13875

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The choice of route of administration should be carefully selected by the clinician according to the individual characteristics of each patient.

Microbiome and metabolic disorders

There is increasing evidence that dysbiosis influences metabolic diseases like obesity and type 2 diabetes mellitus. Through regulation of immune cells, intestinal epithelial cells, satiety 

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Sittipo, P., Lobionda, S., Lee, Y.K. et al. Intestinal microbiota and the immune system in metabolic diseases. J Microbiol. 56, 154–162 (2018). https://doi.org/10.1007/s12275-018-7548-y

​Greenhill C. Obesity: Gut microbiota, host genetics and diet interact to affect the risk of developing obesity and the metabolic syndrome. Nat Rev Endocrinol. 2015 Nov;11(11):630. doi: 10.1038/nrendo.2015.152. Epub 2015 Sep 8. PMID: 26346953.

Wang, D.D., Nguyen, L.H., Li, Y. et al. The gut microbiome modulates the protective association between a Mediterranean diet and cardiometabolic disease risk. Nat Med 27, 333–343 (2021). https://doi.org/10.1038/s41591-020-01223-3

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