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

  • Daniel Selvig
  • Yvette Piceno
  • Jonathan Terdiman
  • Martin Zydek
  • Sarah E. Umetsu
  • Dana Balitzer
  • Doug Fadrosh
  • Kole Lynch
  • Brandon Lamere
  • Tom Leith
  • Zain Kassam
  • Kendall Beck
  • Sara Lewin
  • Averil Ma
  • Ma Somsouk
  • Susan V. Lynch
  • Najwa El-NachefEmail author
Original Article
  • 31 Downloads

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.

Keywords

Pouchitis IBD Microbiome Dysbiosis FMT Fecal microbiota transplantation IPAA 

Notes

Author’s contribution

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.

Funding

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

Compliance with Ethical Standards

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.

Supplementary material

10620_2019_5715_MOESM1_ESM.docx (24 kb)
Supplementary material 1 (DOCX 24 kb)
10620_2019_5715_MOESM2_ESM.docx (31 kb)
Supplementary material 2 (DOCX 31 kb)

References

  1. 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.CrossRefGoogle Scholar
  2. 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).Google Scholar
  3. 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.CrossRefGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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.CrossRefGoogle Scholar
  6. 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.CrossRefGoogle Scholar
  7. 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.CrossRefGoogle Scholar
  8. 8.
    Borody TJ, Khoruts A. Fecal microbiota transplantation and emerging applications. Nat Rev Gastroenterol Hepatol. 2011;9:88–96.CrossRefGoogle Scholar
  9. 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.CrossRefGoogle Scholar
  10. 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.CrossRefGoogle Scholar
  11. 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.CrossRefGoogle Scholar
  12. 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.CrossRefGoogle Scholar
  13. 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.CrossRefGoogle Scholar
  14. 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.CrossRefGoogle Scholar
  15. 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.CrossRefGoogle Scholar
  16. 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. 17.
    Caporaso JG, Kuczynski J, Stombaugh J, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7:335–336.CrossRefGoogle Scholar
  18. 18.
    Lozupone C, Knight R. UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol. 2005;71:8228–8235.CrossRefGoogle Scholar
  19. 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.CrossRefGoogle Scholar
  20. 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.CrossRefGoogle Scholar
  21. 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.CrossRefGoogle Scholar
  22. 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.CrossRefGoogle Scholar
  23. 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.CrossRefGoogle Scholar
  24. 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.CrossRefGoogle Scholar
  25. 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.CrossRefGoogle Scholar
  26. 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.CrossRefGoogle Scholar
  27. 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.CrossRefGoogle Scholar
  28. 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.CrossRefGoogle Scholar
  29. 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.CrossRefGoogle Scholar
  30. 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. 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.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Daniel Selvig
    • 1
  • Yvette Piceno
    • 1
  • Jonathan Terdiman
    • 1
  • Martin Zydek
    • 1
  • Sarah E. Umetsu
    • 2
  • Dana Balitzer
    • 2
  • Doug Fadrosh
    • 1
  • Kole Lynch
    • 1
  • Brandon Lamere
    • 1
  • Tom Leith
    • 3
  • Zain Kassam
    • 3
    • 4
  • Kendall Beck
    • 1
  • Sara Lewin
    • 1
  • Averil Ma
    • 1
  • Ma Somsouk
    • 1
  • Susan V. Lynch
    • 1
  • Najwa El-Nachef
    • 1
    Email author
  1. 1.Division of Gastroenterology, Department of MedicineUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Department of PathologyUniversity of California, San FranciscoSan FranciscoUSA
  3. 3.OpenBiomeSomervilleUSA
  4. 4.Finch Therapeutics GroupSomervilleUSA

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