Korean J Gastroenterol.  2021 Jul;78(1):31-36. 10.4166/kjg.2021.089.

Efficacy and Safety of Fecal Microbiota Transplantation and Prospect of Microbe-based Therapies for Inflammatory Bowel Disease

• Jo HG
• Seo GS

• KMID: 2518748
• DOI: http://doi.org/10.4166/kjg.2021.089

Abstract

The use of 5-ASA, immunomodulators, biologics, and small molecule drugs are the main treatment for inflammatory bowel disease (IBD), however, fecal microbiota transplantation (FMT) is also drawing attention as a treatment to improve intestinal dysbiosis by transplantaing normal human stool into patients with IBD. FMT demonstrates relatively good effects in inducing clinical remission in IBD, but unlike Clostridium difficile infection, multiple FMT can enhance the clinical effect. There are no reports of the long-term effectiveness and safety of FMT conducted in IBD yet, therefore, well-designed, prospective studies will be needed. Gut microbiota can affect inflammatory response, intestinal barrier function, and host metabolism, so microbe-based therapies are likely to be a new treatment option for IBD. The deeper the understanding of microbe products or effectors, the more likely it is to provide personalized therapy in IBD.

Keyword

Fecal microbiota transplantation; Inflammatory bowel diseases; Microbe-based therapies

Reference

1. Murray A, Nguyen TM, Parker CE, Feagan BG, MacDonald JK. 2020; Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 8:CD000544. DOI: 10.1002/14651858.CD000544.pub5. PMID: 32856298.

2. Mantzaris GJ. 2017; Thiopurines and methotrexate use in IBD patients in a biologic era. Curr Treat Options Gastroenterol. 15:84–104. DOI: 10.1007/s11938-017-0128-0. PMID: 28160250.

3. Magro F, Cordeiro G, Dias AM, Estevinho MM. 2020; Inflammatory bowel disease - non-biological treatment. Pharmacol Res. 160:105075. DOI: 10.1016/j.phrs.2020.105075. PMID: 32653651.

4. Ooi CJ, Hilmi I, Banerjee R, et al. 2019; Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia. Intest Res. 17:285–310. DOI: 10.5217/ir.2019.00026. PMID: 31146509. PMCID: PMC6667368.

5. Fukuda T, Naganuma M, Kanai T. 2019; Current new challenges in the management of ulcerative Colitis. Intest Res. 17:36–44. DOI: 10.5217/ir.2018.00126. PMID: 30678445. PMCID: PMC6361009.

6. Al-Bawardy B, Shivashankar R, Proctor DD. 2021; Novel and emerging therapies for inflammatory bowel disease. Front Pharmacol. 12:651415. DOI: 10.3389/fphar.2021.651415. PMID: 33935763. PMCID: PMC8080036.

7. Imdad A, Nicholson MR, Tanner-Smith EE, et al. 2018; Fecal transplantation for treatment of inflammatory bowel disease. Cochrane Database Syst Rev. 11:CD012774. DOI: 10.1002/14651858.CD012774.pub2. PMID: 30480772. PMCID: PMC6517295.

8. Tan P, Li X, Shen J, Feng Q. 2020; Fecal Microbiota transplantation for the treatment of inflammatory bowel disease: an update. Front Pharmacol. 11:574533. DOI: 10.3389/fphar.2020.574533. PMID: 33041818. PMCID: PMC7530266.

9. Haifer C, Leong RW, Paramsothy S. 2020; The role of faecal microbiota transplantation in the treatment of inflammatory bowel disease. Curr Opin Pharmacol. 55:8–16. DOI: 10.1016/j.coph.2020.08.009. PMID: 33035780. PMCID: PMC7538387.

10. Paramsothy S, Paramsothy R, Rubin DT, et al. 2017; Faecal microbiota transplantation for inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis. 11:1180–1199. DOI: 10.1093/ecco-jcc/jjx063. PMID: 28486648.

11. Khoruts A, Sadowsky MJ. 2016; Understanding the mechanisms of faecal microbiota transplantation. Nat Rev Gastroenterol Hepatol. 13:508–516. DOI: 10.1038/nrgastro.2016.98. PMID: 27329806. PMCID: PMC5909819.

12. Enforcement policy regarding investigational new drug requirements for use of fecal microbiota for transplantation to treat Clostridium difficile infection not responsive to standard therapies: draft guidance for industry. [Internet]. 2016. Mar. U. S. Food and Drug Adminstration;Silver Spring (MD): Available from: https://www.fda.gov/media/96562/download. cited 2021 Jun 9.

13. Guidance for industry: enforcement policy regarding investigational new drug requirements for use of fecal microbiota for transplantation to treat Clostridium difficile infection not responsive to standard therapies. [Internet]. 2013. Jul. U. S. Food and Drug Adminstration;Silver Spring (MD): Available from: https://www.fda.gov/media/86440/download. cited 2021 Jun 9.

14. Kelly CR, Kahn S, Kashyap P, et al. 2015; Update on fecal microbiota transplantation 2015: indications, methodologies, mechanisms, and outlook. Gastroenterology. 149:223–237. indications. DOI: 10.1053/j.gastro.2015.05.008. PMID: 25982290. PMCID: PMC4755303.

15. Kelly CR, Kunde SS, Khoruts A. 2014; Guidance on preparing an investigational new drug application for fecal microbiota transplantation studies. Clin Gastroenterol Hepatol. 12:283–288. DOI: 10.1016/j.cgh.2013.09.060. PMID: 24107393. PMCID: PMC3947095.

16. Cammarota G, Ianiro G, Tilg H, et al. 2017; European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 66:569–580. DOI: 10.1136/gutjnl-2016-313017. PMID: 28087657. PMCID: PMC5529972.

17. Cammarota G, Ianiro G, Kelly CR, et al. 2019; International consensus conference on stool banking for faecal microbiota transplantation in clinical practice. Gut. 68:2111–2121. DOI: 10.1136/gutjnl-2019-319548. PMID: 31563878. PMCID: PMC6872442.

18. Mullish BH, Quraishi MN, Segal JP, et al. 2018; The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines. Gut. 67:1920–1941. DOI: 10.1136/gutjnl-2018-316818. PMID: 30154172.

19. Lloyd-Price J, Arze C, Ananthakrishnan AN, et al. 2019; Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature. 569:655–662. DOI: 10.1038/s41586-019-1237-9. PMID: 31142855. PMCID: PMC6650278.

20. Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. 2007; Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. 104:13780–13785. DOI: 10.1073/pnas.0706625104. PMID: 17699621. PMCID: PMC1959459.

21. Cohen LJ, Cho JH, Gevers D, Chu H. 2019; Genetic factors and the intestinal microbiome guide development of microbe-based therapies for inflammatory bowel diseases. Gastroenterology. 156:2174–2189. DOI: 10.1053/j.gastro.2019.03.017. PMID: 30880022. PMCID: PMC6568267.

22. Plichta DR, Graham DB, Subramanian S, Xavier RJ. 2019; Therapeutic opportunities in inflammatory bowel disease: mechanistic dissection of host-microbiome relationships. Cell. 178:1041–1056. DOI: 10.1016/j.cell.2019.07.045. PMID: 31442399. PMCID: PMC6778965.

23. Basso PJ, Câmara NOS, Sales-Campos H. 2019; Microbial-based therapies in the treatment of inflammatory bowel disease - an overview of human studies. Front Pharmacol. 9:1571. DOI: 10.3389/fphar.2018.01571. PMID: 30687107. PMCID: PMC6335320.

24. Zheng D, Liwinski T, Elinav E. 2020; Interaction between microbiota and immunity in health and disease. Cell Res. 30:492–506. DOI: 10.1038/s41422-020-0332-7. PMID: 32433595. PMCID: PMC7264227.

25. Oka A, Sartor RB. 2020; Microbial-based and microbial-targeted therapies for inflammatory bowel diseases. Dig Dis Sci. 65:757–788. DOI: 10.1007/s10620-020-06090-z. PMID: 32006212. PMCID: PMC7311927.

26. Moayyedi P, Surette MG, Kim PT, et al. 2015; Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology. 149:102–109.e6. DOI: 10.1053/j.gastro.2015.04.001. PMID: 25857665.

27. Rossen NG, Fuentes S, van der Spek MJ, et al. 2015; Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology. 149:110–118.e4. DOI: 10.1053/j.gastro.2015.03.045. PMID: 25836986.

28. Paramsothy S, Kamm MA, Kaakoush NO, et al. 2017; Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet. 389:1218–1228. DOI: 10.1016/S0140-6736(17)30182-4.

29. Costello SP, Hughes PA, Waters O, et al. 2019; Effect of fecal microbiota transplantation on 8-week remission in patients with ulcerative colitis: a randomized clinical trial. JAMA. 321:156–164. DOI: 10.1001/jama.2018.20046. PMID: 30644982. PMCID: PMC6439766.

30. Sood A, Mahajan R, Singh A, et al. 2019; Role of faecal microbiota transplantation for maintenance of remission in patients with ulcerative colitis: a pilot study. J Crohns Colitis. 13:1311–1317. DOI: 10.1093/ecco-jcc/jjz060. PMID: 30873549.

31. Sood A, Singh A, Mahajan R, et al. 2020; Aug. 9. Clinical predictors of response to faecal microbiota transplantation in patients with active ulcerative colitis. J Crohns Colitis. [Epub ahead of print]. DOI: 10.1093/ecco-jcc/jjaa163. PMID: 32772093.

32. Sood A, Mahajan R, Juyal G, et al. 2019; Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis. Intest Res. 17:78–86. DOI: 10.5217/ir.2018.00089. PMID: 30449078. PMCID: PMC6361022.

33. Crothers J, Kassam Z, Smith M, et al. 2018; A double-blind, randomized, placebo-control pilot trial of fecal microbiota transplantation capsules from rationally selected donors in active ulcerative colitis. Gastroenterology. 154:S‐1050‐S‐1051. DOI: 10.1016/S0016-5085(18)33519-4.

34. Cui B, Feng Q, Wang H, et al. 2015; Fecal microbiota transplantation through mid-gut for refractory Crohn's disease: safety, feasibility, and efficacy trial results. J Gastroenterol Hepatol. 30:51–58. DOI: 10.1111/jgh.12727. PMID: 25168749.

35. Vaughn BP, Vatanen T, Allegretti JR, et al. 2016; Increased intestinal microbial diversity following fecal microbiota transplant for active Crohn's disease. Inflamm Bowel Dis. 22:2182–2190. DOI: 10.1097/MIB.0000000000000893. PMID: 27542133. PMCID: PMC4995064.

36. Sokol H, Landman C, Seksik P, et al. 2020; Fecal microbiota transplantation to maintain remission in Crohn's disease: a pilot randomized controlled study. Microbiome. 8:12. DOI: 10.1186/s40168-020-0792-5. PMID: 32014035. PMCID: PMC6998149.

37. Xiang L, Ding X, Li Q, et al. 2020; Efficacy of faecal microbiota transplantation in Crohn's disease: a new target treatment? Microb Biotechnol. 13:760–769. DOI: 10.1111/1751-7915.13536. PMID: 31958884. PMCID: PMC7111085.

38. A prospective multicenter randomized controlled trial comparing fecal microbiota transplantation (FMT) to placebo in the treatment of mild to moderate Crohn's disease. [Internet]. 2017. Mar. 13. U. S. Food and Drug Adminstration;Silver Spring (MD): Available from: https://clinicaltrials.gov/ct2/show/NCT03078803. updated 2020 May 12; cited 2021 Jun 9.

39. Vermeire S, Joossens M, Verbeke K, et al. 2016; Donor species richness determines faecal microbiota transplantation success in inflammatory bowel disease. J Crohns Colitis. 10:387–394. DOI: 10.1093/ecco-jcc/jjv203. PMID: 26519463. PMCID: PMC4946755.

40. DeFilipp Z, Bloom PP, Torres Soto M, et al. 2019; Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant. N Engl J Med. 381:2043–2050. DOI: 10.1056/NEJMoa1910437. PMID: 31665575.

41. Xu CLH, Raval M, Schnall JA, Kwong JC, Holmes NE. 2020; Duration of respiratory and gastrointestinal viral shedding in children with SARS-CoV-2: a systematic review and synthesis of data. Pediatr Infect Dis J. 39:e249–e256. DOI: 10.1097/INF.0000000000002814. PMID: 32618932.

42. Brogna B, Brogna C, Petrillo M, et al. 2021; SARS-CoV-2 detection in fecal sample from a patient with typical findings of COVID-19 pneumonia on CT but negative to multiple SARS-CoV-2 RT-PCR tests on oropharyngeal and nasopharyngeal swab samples. Medicina (Kaunas). 57:290. DOI: 10.3390/medicina57030290. PMID: 33804646. PMCID: PMC8003654.

43. Haifer C, Kelly CR, Paramsothy S, et al. 2020; Australian consensus statements for the regulation, production and use of faecal microbiota transplantation in clinical practice. Gut. 69:801–810. DOI: 10.1136/gutjnl-2019-320260. PMID: 32047093.

44. Dreher-Lesnick SM, Stibitz S, Carlson PE Jr. 2017; U.S. regulatory considerations for development of live biotherapeutic products as drugs. Microbiol Spectr. 5:doi: 10.1128/microbiolspec. BAD-0017-2017. DOI: 10.1128/microbiolspec.