Skip to main content
SpringerLink
Log in

Fecal Microbiota Transplantation in Pouchitis: Clinical, Endoscopic, Histologic, and Microbiota Results from a Pilot Study

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Aims

This pilot study assessed the efficacy, safety, and microbiome dynamics of fecal microbiota transplantation (FMT) for patients with chronic pouchitis.

Methods

A prospective open-label pilot study was performed at an academic center among pouchitis patients undergoing FMT. Patients received a minimum of a single FMT by pouchoscopy from healthy, screened donors. The primary outcome was clinical improvement in pouchitis assessed by patient survey at week 4. Secondary outcomes included decrease in total Pouchitis Disease Activity Index (PDAI) Score ≥ 3 at week 4, bowel movement frequency, ESR, CRP, fecal calprotectin, abdominal pain, and PDAI subscores including endoscopic and histologic changes. Stool samples were collected at baseline and 4 weeks post-FMT to assess bacterial microbiota using V4 16S rRNA sequencing.

Results

Nineteen patients were enrolled; however, 1 patient was lost to follow-up. No patients had a major adverse event or escalation of therapy related to FMT. Total PDAI scores, endoscopic scores, and histologic scores did not decrease significantly post-FMT. However, there was a statistically significant improvement in bowel movement (BM) frequency (9.25–7.25 BM/day, p = 0.03) and trend for improvement in abdominal pain to improve post-FMT (p = 0.05). Bacterial microbiota profiling revealed no distinct community-level changes post-FMT, though a small number of specific bacterial taxa significantly differed in relative abundance.

Conclusions

A single FMT has a tolerable short-term safety profile and may be associated with a decrease in bowel movements in patients with chronic pouchitis; however, no robust endoscopic or histologic changes were observed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Farouk R, Pemberton JH, Wolff BG, Dozois RR, Browning S, Larson D. Functional outcomes after ileal pouch-anal anastomosis for chronic ulcerative colitis. Ann Surg. 2000;231:919–926.

    Article  CAS  Google Scholar 

  2. Hahnloser D, Pemberton JH, Wolff BG, Larson DR, Crownhart BS, Dozois RR. The effect of ageing on function and quality of life in ileal pouch patients: a single cohort experience of 409 patients with chronic ulcerative colitis. Ann Surg. 2004;240:615–621. (discussion 621–623).

    PubMed  PubMed Central  Google Scholar 

  3. Meagher AP, Farouk R, Dozois RR, Kelly KA, Pemberton JH. J ileal pouch-anal anastomosis for chronic ulcerative colitis: complications and long-term outcome in 1310 patients. Br J Surg. 1998;85:800–803.

    Article  CAS  Google Scholar 

  4. Penna C, Dozois R, Tremaine W, et al. Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis. Gut. 1996;38:234–239.

    Article  CAS  Google Scholar 

  5. Fazio VW, Ziv Y, Church JM, et al. Ileal pouch-anal anastomoses complications and function in 1005 patients. Ann Surg. 1995;222:120–127.

    Article  CAS  Google Scholar 

  6. Mimura T, Rizzello F, Helwig U, et al. Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut. 2004;53:108–114.

    Article  CAS  Google Scholar 

  7. Gionchetti P, Rizzello F, Helwig U, et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology. 2003;124:1202–1209.

    Article  Google Scholar 

  8. Borody TJ, Khoruts A. Fecal microbiota transplantation and emerging applications. Nat Rev Gastroenterol Hepatol. 2011;9:88–96.

    Article  Google Scholar 

  9. Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol. 2013;108:500–508.

    Article  Google Scholar 

  10. Narula N, Kassam Z, Yuan Y, et al. Systematic review and meta-analysis: fecal microbiota transplantation for treatment of active ulcerative colitis. Inflamm Bowel Dis. 2017;23:1702–1709.

    Article  Google Scholar 

  11. Stallmach A, Lange K, Buening J, Sina C, Vital M, Pieper DH. Fecal microbiota transfer in patients with chronic antibiotic-refractory pouchitis. Am J Gastroenterol. 2016;111:441–443.

    Article  Google Scholar 

  12. Landy J, Walker AW, Li JV, et al. Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis. Sci Rep. 2015;12:12955.

    Article  Google Scholar 

  13. Fang S, Kraft CS, Dhere T, et al. Successful treatment of chronic pouchitis utilizing fecal microbiota transplantation (FMT): a case report. Int J Colorectal Dis. 2016;31:1093–1094.

    Article  Google Scholar 

  14. Schmid M, Frick J-S, Malek N, Goetz M. Successful treatment of pouchitis with Vedolizumab, but not fecal microbiota transfer (FMT), after proctocolectomy in ulcerative colitis. Int J Colorectal Dis. 2017;32:597–598.

    Article  Google Scholar 

  15. Burns LJ, Dubois N, Smith MB, et al. 499 Donor recruitment and eligibility for fecal microbiota transplantation: results from an international public stool bank. Gastroenterology. 2015;148:S96–S97.

    Article  Google Scholar 

  16. R Core Team. R: A Language and Environment for Statistical Computing. Vienna: R Foundation for Statistical Computing; 2017. https://www.R-project.org.

  17. Caporaso JG, Kuczynski J, Stombaugh J, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7:335–336.

    Article  CAS  Google Scholar 

  18. Lozupone C, Knight R. UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol. 2005;71:8228–8235.

    Article  CAS  Google Scholar 

  19. Romero R, Hassan SS, Gajer P, et al. Correction: the composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women. Microbiome. 2014;2:10.

    Article  Google Scholar 

  20. McLaughlin SD, Walker AW, Churcher C, et al. The bacteriology of pouchitis: a molecular phylogenetic analysis using 16S rRNA gene cloning and sequencing. Ann Surg. 2010;252:90–98.

    Article  Google Scholar 

  21. Tannock GW, Lawley B, Munro K, et al. Comprehensive analysis of the bacterial content of stool from patients with chronic pouchitis, normal pouches, or familial adenomatous polyposis. Inflamm Bowel Dis. 2012;18:925–934.

    Article  Google Scholar 

  22. Angriman I, Scarpa M, Castagliuolo I. Relationship between pouch microbiota and pouchitis following restorative proctocolectomy for ulcerative colitis. World J Gastroenterol. 2014;20:9665–9674.

    Article  Google Scholar 

  23. Morgan XC, Kabakchiev B, Waldron L, et al. Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease. Genome Biol. 2015;8:67.

    Article  Google Scholar 

  24. Moayyedi P, Surette MG, Kim PT, et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology. 2015;149:102–109.e6.

    Article  Google Scholar 

  25. Paramsothy S, Kamm MA, Kaakoush NO, et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet. 2017;389:1218–1228.

    Article  Google Scholar 

  26. Yadav A, Foromera J, Falchuk KR, Feuerstein JD. Biologics and immunomodulators for treating Crohn’s disease developing after surgery for an initial diagnosis of ulcerative colitis: a review of current literature. Scand J Gastroenterol. 2018;53:813–817.

    Article  CAS  Google Scholar 

  27. Madden MV, McIntyre AS, Nicholls RJ. Double-blind crossover trial of metronidazole versus placebo in chronic unremitting pouchitis. Dig Dis Sci. 1994;39:1193–1196.

    Article  CAS  Google Scholar 

  28. Shen B, Achkar J-P, Lashner BA, et al. Irritable pouch syndrome: a new category of diagnosis for symptomatic patients with ileal pouch-anal anastomosis. Am J Gastroenterol. 2002;97:972–977.

    Article  Google Scholar 

  29. Dethlefsen L, Huse S, Sogin ML, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 2008;6:e280.

    Article  Google Scholar 

  30. Shen B, Remzi FH, Lopez AR, Queener E. Rifaximin for maintenance therapy in antibiotic-dependent pouchitis. BMC Gastroenterol. 2008;7:1–7.

    Google Scholar 

  31. Isaacs KL, Sandler RS, Abreu M, et al. Rifaximin for the treatment of active pouchitis: A randomized, double-blind placebo-controlled pilot study. Inflamm Bowel Dis. 2007;13:1250–1255.

    Article  Google Scholar 

Download references

Funding

Philanthropic Gift. The study design, data collection, analysis, and interpretation were performed independently of the funding source.

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA

    Daniel Selvig, Yvette Piceno, Jonathan Terdiman, Martin Zydek, Doug Fadrosh, Kole Lynch, Brandon Lamere, Kendall Beck, Sara Lewin, Averil Ma, Ma Somsouk, Susan V. Lynch & Najwa El-Nachef

  2. Department of Pathology, University of California, San Francisco, San Francisco, CA, USA

    Sarah E. Umetsu & Dana Balitzer

  3. OpenBiome, Somerville, MA, USA

    Tom Leith & Zain Kassam

  4. Finch Therapeutics Group, Somerville, MA, USA

    Zain Kassam

Authors
  1. Daniel Selvig
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yvette Piceno
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jonathan Terdiman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin Zydek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sarah E. Umetsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dana Balitzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Doug Fadrosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kole Lynch
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Brandon Lamere
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tom Leith
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zain Kassam
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kendall Beck
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Sara Lewin
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Averil Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Ma Somsouk
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Susan V. Lynch
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Najwa El-Nachef
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

DS contributed to analysis and interpretation of the data, drafting of the manuscript, and critical revision of the manuscript. YP contributed to microbial sample processing and analysis, drafting of the manuscript, analysis and interpretation of the data. DF, KL, and BL contributed to microbial sequencing. MZ contributed to study supervision, data collection, and regulatory submissions. KB and SL provided blinded endoscopy scores. SU and DB provided blinded histology scores. TL contributed to data collection, regulatory submission, and intervention operations. ZK and JT contributed to study concept and design, and critical revision of the manuscript. AM conceived and designed the study. MS analyzed and interpreted the data. SL contributed to microbial analysis and critical revision of the manuscript. NE-N contributed to study concept and design, principal investigator, and critical revision of the manuscript.

Corresponding author

Correspondence to Najwa El-Nachef.

Ethics declarations

Conflict of interest

ZK is currently an employee and shareholder of Finch Therapeutics Group. ZK and TL were employees of the nonprofit stool bank, OpenBiome, at the time of the study. SVL co-founded, is a shareholder, is on the board of directors and acts as a consultant for Siolta Therapeutics, and is a scientific advisory board member for Bloom Science.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Guarantor of the article: Najwa El-Nachef.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 24 kb)

Supplementary material 2 (DOCX 31 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Selvig, D., Piceno, Y., Terdiman, J. et al. Fecal Microbiota Transplantation in Pouchitis: Clinical, Endoscopic, Histologic, and Microbiota Results from a Pilot Study. Dig Dis Sci 65, 1099–1106 (2020). https://doi.org/10.1007/s10620-019-05715-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-019-05715-2

Keywords

Search

Navigation