By: Dr. Shaina Cahill, Ph.D. (Director Medical Communications & Affairs)
Fecal microbiota transplantation (FMT) is an approved treatment for recurrent Clostridioides difficile infection (rCDI). FMT has been shown to be highly effective, leading to its increased use experimentally in both gastrointestinal (GI) and non-GI disorders 1, such as inflammatory bowel disease (IBD) 2–4, irritable bowel syndrome (IBS)5–7, metabolic disorders 8–13, autism spectrum disorder 14–16, Parkinson’s disease 17–19, and multiple sclerosis 20 (To learn more about FMT, check out our What is FMT blog).
FMT administration can be categorized into either upper or lower GI routes 1,21–25. The preferred route of administration for FMT remains a topic of discussion, and the most optimal method of administration remains unclear 22,26. Studies suggested that lower gastrointestinal FMT delivery may be preferable to upper gastrointestinal FMT delivery 25. However, the evidence is somewhat divided on if upper GI or lower GI FMT administration is superior. In addition, the recent creation of FMT capsules which show comparable efficacy to lower GI methods, such as colonoscopy, combined with their convenience and safety, have made them an increasingly attractive option 1,21,23,26–35. In addition, several stool preparations are utilized for FMT, including fresh, frozen and thawed, and lyophilized preparations 36
Upper GI administration
Standard methods of upper gastrointestinal administration for FMT include a nasogastric tube, nasoduodenal tube, a nasojejunal tube and FMT capsules taken orally 26. Generally, upper GI administration is faster, less expensive and requires less stool compared to lower GI routes and success rates are reported to be around 80% 26,28,37,38. Both nasogastric and nasoduodenal tubes are not usually the preferred route of FMT delivery; in contrast, the use of FMT capsules is on the rise 31,35,39,40.
The most recent development in FMT administration is the creation of FMT capsules which involve double- or triple-encapsulation of prepared donor stool, which is administered to patients in capsule form 26,27,31,35. FMT capsules are minimally invasive, safe, and rated as the preferred mode of administration by patients 1,21,26–28,41–44. Research has shown that FMT capsules used to treat rCDI are highly effective and safe, with efficacy comparable to FMT delivered through other routes, including colonoscopy 1,21,23,27–35. Initial studies have reported efficacy rates for FMT capsules to be over 80% after a single dose which increases to around 90% after multiple treatments 1,21,27,28,30,33,40,45.
The risks of upper GI administration (not including capsules) include regurgitation, vomiting, aspiration, hemorrhage and perforation of the upper gastrointestinal system 26,28,46–48. Adverse events are reported to be more common for upper GI than lower GI administration (43.6% vs. 17.7%) 26,28,34,40. Specific to FMT capsules, adverse events are reported to be mild and transient gastrointestinal symptoms, including diarrhea, nausea, abdominal discomfort and bloating, which resolve quickly without intervention 21,27,35. Generally, adverse events for FMT capsules are reported to be lower than in other modes of FMT administration 29,30,32–34. Overall, FMT capsules provide increased safety over other administration methods by removing the need for invasive procedures and removing procedure-associated complications 1,27.
Lower GI methods
Lower gastrointestinal administration includes colonoscopy and retention enemas 26. Generally, lower GI administration successfully treats rCDI, with success rates ranging from 84% to 93% 28,49. While more studies comparing FMT administration methods are needed, initial research suggests that colonoscopy affords better success rates than upper GI administration (91.4% vs 82.3%) 28,49.
While lower GI administration is well-tolerated and safe, there are increased costs and risks due to the inherently invasive nature of these procedures 28. There is a risk of bowel perforation for colonoscopy, and those who are severely ill may not tolerate the procedure or anesthesia 26,50–52. Retention enemas are less invasive and easier to perform with reported adverse events, including transient diarrhea, flatulence, abdominal pain/cramping, and constipation 26,42,53. The most considerable concerns with retention enemas are stool retention and where stool is deposited 26,54. While lower GI tract administration does carry some inherent risks, it remains the most common delivery method given the wealth of data supporting its efficacy 28,49,55.
How do the different administration methods compare?
Currently, the evidence is somewhat divided on if upper or lower GI FMT administration is superior. With reports concluding in some cases that lower GI administration is more effective 24,31,32,32,36,40,45,49,53,54,56–60 while in others, no significant difference between the effectiveness of upper and lower GI administration is found 24,26,27,33,61–63. Colonoscopy is still considered the gold standard for FMT administration, as it is still the most common administration method and has a wealth of data and efficacy rates reported over 90% 24,28,32,49,54,55,57–59. But, FMT capsules have been reported to be highly successful, safe, non-invasive and require fewer resources than colonoscopy1,26,40,41,43. In addition, FMT capsules have consistently shown to be as effective and increase microbial diversity, similar to colonoscopy 1,21,23,27–35. Patients rate FMT via capsules as more pleasant and their preferred route of administration 1,27,31,41,43. Overall, the creation of FMT capsules may allow FMT to be more accessible and aesthetically pleasing for patients and become the standard of care.
Our focus at Novel Biome is on supporting autistic children who suffer from digestive symptoms and significant microbiome imbalance to restore their microbiome through Fecal Microbiota Transplantation (FMT). We offer different forms of FMT administration, including retention enema, oral capsules and oral powder, allowing us to tailor treatment to each patient.
Team Novel Biome
References: 1. Cold, F. et al. 2021, 2. Aldars-García, L. et al. 2021, 3. Anderson, J. L. et al. 2012, 4. Tan, P. et al. 2020, 5. Cruz-Aguliar, R. M. et al. 2019, 6. El-Salhy, M. et al. 2022, 7. Ianiro, G. et al. 2019, 8. Allegretti, J. R. et al. 2021, 9. Kootte, R. S. et al. 2017, 10. Proença, I. M. et al. 2020, 11. Rinott, E. et al. 2021, 12. Rinott, E. et al. 2021, 13. Zhang et al. 2019, 14. Kang, D.-W. et al. 2017, 15. Kang, D.-W. et al. 2019, 16. Li, N. et al. 2021, 17. Huang, H. et al. 2019, 18. Segal, A. et al. 2021, 19. Sun, M.-F. et al. 2018, 20. Makkawi, S. et al. 2018, 21. Hirsch, B. E. et al. 2015, 22. Ooijevaar, R. E. et al. 2019, 23. Ramai, D. et al. 2021, 24. Smits, L. et al. 2013, 25. Tang, G., et al. 2017, 26. Ramai, D. 2018, 27. Youngster, I. et al. 2014, 28. Krajicek, E., et al. 2019, 29. Baxter, M. & Colville, A. 2016, 30. Iqbal, U. et al. 2018, 31. Kao, D. et al. 2017, 32. Postigo, R. & Kim, J. H. 2012, 33. Reigadas, E. et al. 2020, 34. Wang, S. et al. 2016, 35. Youngster, I. et al. 2016, 36. Gerardin, Y. et al. 2021, 37. Bakken, J. S. 2009, 38. Garborg, K. et al. 2010, 39. Cammarota, G. et al. 2014, 40. Fadda, H. M. 2020, 41. Kassam, Z. et al. 2015, 42. Khanna, S. 2018, 43. Roggenbrod, S. et al. 2019, 44. Zipursky, J. S. et al. 2012, 45. Ianiro, G. et al. 2018, 46. Baxter, M. et al. 2015, 47. Hagel, S. et al. 2016, 48. Van Beurden, Y. H. et al. 2016, 49. Kassam, Z. et al. 2013, 50. Kelly, C. R. et al. 2014, 51. Pathak, R. et al. 2013, 52. Zainah, H. et al. 2015, 53. Kassam, Z. 2012, 54. Persky, S. E. & Brandt, L. 2000, 55. Drekonja, D. et al. 2015, 56. Kelly, C. R. 2012, 57. Rohlke, F. et al. 2010, 58. Yoon, S. S. & Brandt, L. J. 2010, 59. Gough, E. et al. 2011, 60. Narula, N. et al. 2017, 61. van Nood, E. et al. 2013, 62. Quraishi, M. N. et al. 2017, 63. Youngster, I. et al. 2014.