Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis

Yanqiang Shi, Yiwei Dong, Wenhui Huang, Decong Zhu, Hua Mao, Peizhu Su, Yanqiang Shi, Yiwei Dong, Wenhui Huang, Decong Zhu, Hua Mao, Peizhu Su

Abstract

Background: Fecal microbiota transplantation (FMT) has been recognized as a novel treatment for ulcerative colitis (UC). However, its efficacy and safety remain unclear.

Objective: We conducted this systematic review to assess the efficacy and safety of FMT in UC.

Data sources: PubMed, EMBASE, Cochrane Central, Web of Science Core Collection, and three other Chinese databases were searched for reports of FMT in UC with clear outcomes.

Data extraction and synthesis: We estimated pooled rates [with 95% confidence interval (CI)] of clinical remission among 15 cohort studies and clinical response among 16 cohort studies.

Results: Twenty five studies (2 randomized controlled trials, 15 cohort studies, and 8 case studies) with 234 UC patients were included. Overall, 41.58% (84/202) patients achieved clinical remission (CR) and 65.28% (126/193) achieved clinical response. Among the cohort studies, the pooled estimate of patients who achieved CR and clinical response were 40.5% (95% CI 24.7%-58.7%), and 66.1% (95% CI 43.7%-83.0%). Most adverse events were slight and self-resolving. The analyses of gut microbiota in 7 studies showed that FMT could increase microbiota diversity and richness, similarity, and certain change of bacterial composition.

Conclusion: FMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Flow chart of studies of…
Fig 1. Flow chart of studies of fecal microbiota transplantation in ulcerative colitis.
Fig 2. Forest plot of all cohort…
Fig 2. Forest plot of all cohort studies in clinical remission.
Pooled estimate of 40.5% (95% CI 24.7%-60.4%).
Fig 3. Forest plot of all cohort…
Fig 3. Forest plot of all cohort studies in clinical response.
Pooled estimate of 66.1% (95% CI 43.7%-83.0%).

References

    1. Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med. 2011;365(18):1713–25. 10.1056/NEJMra1102942 .
    1. Stange EF, Travis SP, Vermeire S, Reinisch W, Geboes K, Barakauskiene A, et al. European evidence-based Consensus on the diagnosis and management of ulcerative colitis: Definitions and diagnosis. J Crohns Colitis. 2008;2(1):1–23. 10.1016/j.crohns.2007.11.001 .
    1. Rao SS, Holdsworth CD, Read NW. Symptoms and stool patterns in patients with ulcerative colitis. Gut. 1988;29(3):342–5.
    1. Berg D, Clemente JC, Colombel J-F. Can inflammatory bowel disease be permanently treated with short-term interventions on the microbiome? Expert review of gastroenterology & hepatology. 2015;9(6):781–95. 10.1586/17474124.2015.1013031 .
    1. Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. 2007;104(34):13780–5. Epub 2007/08/19. 10.1073/pnas.0706625104 ; PubMed Central PMCID: PMCPmc1959459.
    1. Sartor RB. Microbial Influences in Inflammatory Bowel Diseases. Gastroenterology. 2008;134(2):577–94. 10.1053/j.gastro.2007.11.059
    1. Hold GL, Smith M, Grange C, Watt ER, El-Omar EM, Mukhopadhya I. Role of the gut microbiota in inflammatory bowel disease pathogenesis: what have we learnt in the past 10 years? World journal of gastroenterology: WJG. 2014;20(5):1192–210. 10.3748/wjg.v20.i5.1192 .
    1. Bringiotti R, Ierardi E, Lovero R, Losurdo G, Di Leo A, Principi M. Intestinal microbiota: The explosive mixture at the origin of inflammatory bowel disease? World journal of gastrointestinal pathophysiology. 2014;5(4):550–9. Epub 2014/11/18. 10.4291/wjgp.v5.i4.550 ; PubMed Central PMCID: PMCPmc4231519.
    1. Bartosch S, Fite A, Macfarlane GT, McMurdo ME. Characterization of bacterial communities in feces from healthy elderly volunteers and hospitalized elderly patients by using real-time PCR and effects of antibiotic treatment on the fecal microbiota. Applied and environmental microbiology. 2004;70(6):3575–81. Epub 2004/06/09. 10.1128/aem.70.6.3575-3581.2004 ; PubMed Central PMCID: PMCPmc427772.
    1. Macfarlane S, Macfarlane GT. Bacterial diversity in the human gut. Advances in applied microbiology. 2004;54:261–89. Epub 2004/07/15. 10.1016/s0065-2164(04)54010-8 .
    1. Cammarota G, Ianiro G, Cianci R, Bibbo S, Gasbarrini A, Curro D. The involvement of gut microbiota in inflammatory bowel disease pathogenesis: potential for therapy. Pharmacology & therapeutics. 2015;149:191–212. Epub 2015/01/07. 10.1016/j.pharmthera.2014.12.006 .
    1. Negroni A, Costanzo M, Vitali R, Superti F, Bertuccini L, Tinari A, et al. Characterization of adherent-invasive Escherichia coli isolated from pediatric patients with inflammatory bowel disease. Inflammatory Bowel Diseases. 2012;18(5):913–24. 10.1002/ibd.21899
    1. Sood A, Midha V, Makharia GK, Ahuja V, Singal D, Goswami P, et al. The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association. 2009;7(11):1202–9, 9, e1 Epub 2009/07/28. 10.1016/j.cgh.2009.07.016 .
    1. Tursi A, Brandimarte G, Papa A, Giglio A, Elisei W, Giorgetti GM, et al. Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study. American journal of gastroenterology [Internet]. 2010; 105(10):[2218–27 pp.]. Available: . 10.1038/ajg.2010.218
    1. Oliva S, Di Nardo G, Ferrari F, Mallardo S, Rossi P, Patrizi G, et al. Randomised clinical trial: the effectiveness of Lactobacillus reuteri ATCC 55730 rectal enema in children with active distal ulcerative colitis. Alimentary Pharmacology & Therapeutics. 2012;35(3):327–34. 10.1111/j.1365-2036.2011.04939.x BIOABS:BACD201200081102.
    1. Zhang F, Luo W, Shi Y, Fan Z, Ji G. Should we standardize the 1,700-year-old fecal microbiota transplantation? The American journal of gastroenterology. 2012;107(11):1755; author reply p.-6. Epub 2012/11/20. 10.1038/ajg.2012.251 .
    1. Eiseman B, Silen W, Bascom GS, Kauvar AJ. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958;44(5):854–9. Epub 1958/11/01. .
    1. Cammarota G, Masucci L, Ianiro G, Bibbo S, Dinoi G, Costamagna G, et al. Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015;41(9):835–43. Epub 2015/03/03. 10.1111/apt.13144 .
    1. 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(4):500–8. Epub 2013/03/21. 10.1038/ajg.2013.59 .
    1. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407–15. Epub 2013/01/18. 10.1056/NEJMoa1205037 .
    1. Cammarota G, Ianiro G, Gasbarrini A. Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review. J Clin Gastroenterol. 2014;48(8):693–702. Epub 2014/01/21. 10.1097/mcg.0000000000000046 .
    1. Moayyedi P, Surette MG, Kim PT, Libertucci J, Wolfe M, Onischi C, et al. Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology. 2015;149(1):102–9. 10.1053/j.gastro.2015.04.001 BIOABS:BACD201500399126.
    1. Rossen NG, Fuentes S, Van Der Spek MJ, Tijssen JG, Hartman JHA, Duflou A, et al. Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. Gastroenterology. 2015;149(1):110–8. 10.1053/j.gastro.2015.03.045
    1. Colman RJ, Rubin DT. Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. Journal of Crohn's & colitis. 2014;8(12):1569–81. 10.1016/j.crohns.2014.08.006 .
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097 Epub 2009/07/22. 10.1371/journal.pmed.1000097 ; PubMed Central PMCID: PMCPmc2707599.
    1. Anderson JL, Edney RJ, Whelan K. Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease. Alimentary Pharmacology & Therapeutics. 2012;36(6):503–16. 10.1111/j.1365-2036.2012.05220.x BIOABS:BACD201200414707.
    1. Higgins JPT A D, Sterne JAC. (eds). Chapter 8: assessing risk of bias in included studies In: Higgins JPT, Green S(eds). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available: . Accessed 8 Aug 2014.
    1. Wells GA SB OCD, Peterson J, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available: Accessed 8 Aug 2014.
    1. Dekkers OM, Egger M, Altman DG, Vandenbroucke JP. Distinguishing case series from cohort studies. Ann Intern Med. 2012;156(1 Pt 1):37–40. Epub 2012/01/04. 10.7326/0003-4819-156-1-201201030-00006 .
    1. DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled clinical trials. 1986;7(3):177–88. Epub 1986/09/01. .
    1. Wallace BC, Schmid CH, Lau J, Trikalinos TA. Meta-Analyst: software for meta-analysis of binary, continuous and diagnostic data. BMC Med Res Methodol. 2009;9:80 Epub 2009/12/08. 10.1186/1471-2288-9-80 ; PubMed Central PMCID: PMCPmc2795760.
    1. Scaldaferri F, Pecere S, Bruno G, Ianiro G, Laterza L, Gerardi V, et al. Tu1363 An Open-Label, Pilot Study to Assess Feasibility and Safety of Fecal Microbiota Transplantation in Patients With Mild-Moderate Ulcerative Colitis: Preliminary Results. Gastroenterology. 148(4):S-870 10.1016/S0016-5085(15)32950-4
    1. Borody T, Wettstein A, Campbell J, Leis S, Torres M, Finlayson S, et al. Fecal microbiota transplantation in ulcerative colitis: Review of 24 years experience. American Journal of Gastroenterology. 2012;107:S665.
    1. Angelberger S, Reinisch W, Makristathis A, Lichtenberger C, Dejaco C, Papay P, et al. Temporal Bacterial Community Dynamics Vary Among Ulcerative Colitis Patients After Fecal Microbiota Transplantation. American Journal of Gastroenterology. 2013;108(10):1620–30. 10.1038/ajg.2013.257 BIOABS:BACD201300498485.
    1. Kump PK, Grochenig HP, Lackner S, Trajanoski S, Reicht G, Hoffmann KM, et al. Alteration of intestinal dysbiosis by fecal microbiota transplantation does not induce remission in patients with chronic active ulcerative colitis. Inflamm Bowel Dis. 2013;19(10):2155–65. Epub 2013/08/01. 10.1097/MIB.0b013e31829ea325 .
    1. Kunde S, Pham A, Bonczyk S, Crumb T, Duba M, Conrad H Jr., et al. Safety, Tolerability, and Clinical Response After Fecal Transplantation in Children and Young Adults With Ulcerative Colitis. JPGN Journal of Pediatric Gastroenterology and Nutrition. 2013;56(6):597–601. 10.1097/MPG.0b013e318292fa0d BIOABS:BACD201300332942.
    1. Landy J, Al-Hassi HO, Mann ER, Peake ST, McLaughlin SD, Ciclitira PJ, et al. A prospective controlled pilot study of fecal microbiota transplantation for chronic refractory pouchitis. Gastroenterology. 2013;144(5):S897.
    1. PK Kump HPGc, W. Spindelbo¨ ck CM Hoffmann G, Gorkiewicz H. Wenzl1, W. Petritsch, G. Reicht, C. Hoegenauer. OP187 PRELIMINARY CLINICAL RESULTS OF REPEATEDLY FECAL MICROBIOTA TRANSPLANTATION (FMT) IN CHRONIC ACTIVE ULCERATIVE COLITIS. 2013.
    1. Wang Mei WK-y, Ding Yan-bing, Wu Jian, Xiao Wei-ming, Li Gui-qing, Wang Ning-zhi, et al. Preliminary clinical application of treating refractory inflammation bowel disease with fecal microbiota transplantation Chinese Journal of Digestive Endoscopy. 2014.
    1. Damman CJ, Brittnacher MJ, Westerhoff M, Hayden HS, Radey M, Hager KR, et al. Low Level Engraftment and Improvement following a Single Colonoscopic Administration of Fecal Microbiota to Patients with Ulcerative Colitis. PLoS One. 2015;10(8):e0133925 Epub 2015/08/20. 10.1371/journal.pone.0133925 .
    1. Kellermayer R, Nagy-Szakal D, Harris RA, Luna RA, Pitashny M, Schady D, et al. Serial Fecal Microbiota Transplantation Alters Mucosal Gene Expression in Pediatric Ulcerative Colitis. American Journal of Gastroenterology. 2015;110(4):604–6. 10.1038/ajg.2015.19 BIOABS:BACD201500302376.
    1. Ren R, Sun G, Yang Y, Peng L, Zhang X, Wang S, et al. [A pilot study of treating ulcerative colitis with fecal microbiota transplantation]. Zhonghua Nei Ke Za Zhi. 2015;54(5):411–5. Epub 2015/06/18. .
    1. Suskind DL, Singh N, Nielson H, Wahbeh G. Fecal Microbial Transplant Via Nasogastric Tube for Active Pediatric Ulcerative Colitis. JPGN Journal of Pediatric Gastroenterology and Nutrition. 2015;60(1):27–9. 10.1097/mpg.0000000000000544 BIOABS:BACD201500176484.
    1. Wei Y, Zhu W, Gong J, Guo D, Gu L, Li N, et al. Fecal Microbiota Transplantation Improves the Quality of Life in Patients with Inflammatory Bowel Disease. Gastroenterology research and practice. 2015;2015:517597- 10.1155/2015/517597 .
    1. Cui B, Li P, Xu L, Zhao Y, Wang H, Peng Z, et al. Step-up fecal microbiota transplantation strategy: a pilot study for steroid-dependent ulcerative colitis. J Transl Med. 2015;13:298 10.1186/s12967-015-0646-2
    1. Karolewska-Bochenek K. L-P I, Grzesiowski P., Banaszkiewicz A. A P, Gawronska A., Radzikowski A., Kotowska M. P427. Fecal microbiota transplantation in refractory pediatric UC—preliminary data. Journal of Crohn's & colitis. 2015;9 Suppl 1:S294–S. 10.1093/ecco-jcc/jju027.546
    1. Bennet JD, Brinkman M. Treatment of ulcerative colitis by implantation of normal colonic flora. Lancet. 1989;1(8630):164.
    1. Borody TJ, George L, Andrews P, Brandl S, Noonan S, Cole P, et al. Bowel-flora alteration: a potential cure for inflammatory bowel disease and irritable bowel syndrome? The Medical journal of Australia. 1989;150(10):604 Epub 1989/05/15. .
    1. Borody TJ, Warren EF, Leis S, Surace R, Ashman O. Treatment of ulcerative colitis using fecal bacteriotherapy. Journal of clinical gastroenterology. 2003;37(1):42–7. 10.1097/00004836-200307000-00012 .
    1. Borody T, Campbell J, Torres M, Nowak A, Leis S. Reversal of idiopathic thrombocytopenic purpura [ITP] with fecal microbiota transplantation [FMT]. American Journal of Gastroenterology. 2011;106:S352.
    1. Liu Chang-qin WW, Wu Rui-jin, Tang Mao-chun, Qiu Hua-jing, Chen Teng-fei, Yang Xue-hua, et al. A case report of fecal microbiota transplantation from healthy volunteer treating ulcerative colitis. Chinese Journal of Digestion. 2013.
    1. Hohmann EL, Ananthakrishnan AN, Deshpande V. Case 25–2014: A 37-Year-Old Man with Ulcerative Colitis and Bloody Diarrhea. New England Journal of Medicine. 2014;371(7):668–75. 10.1056/NEJMcpc1400842 BIOABS:BACD201400502132.
    1. NI X-d, Li Y-s, Zhang Y-l, Tao S, Wang Z-m, LI J-s. Enteral nutrition fecal microbiota transplantation via percutaneous endoscopic cecostomy in treatment of recurrent ulcerative colitis. Parental & Enteral Nutrition. 2015;22:29–38.
    1. Vandenplas Y, Veereman G, van der Werff ten Bosch J, Goossens A, Pierard D, Samsom JN, et al. Fecal Microbial Transplantation in Early-Onset Colitis: Caution Advised. Journal of Pediatric Gastroenterology and Nutrition. 2015;61(3):e12–e4. 10.1097/mpg.0000000000000281 00005176-201509000-00023.
    1. Kelly CR, Kahn S, Kashyap P, Laine L, Rubin D, Atreja A, et al. Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook. Gastroenterology. 2015;149(1):223–37. Epub 2015/05/20. 10.1053/j.gastro.2015.05.008 .
    1. Damman CJ, Miller SI, Surawicz CM, Zisman TL. The microbiome and inflammatory bowel disease: is there a therapeutic role for fecal microbiota transplantation? Am J Gastroenterol. 2012;107(10):1452–9. Epub 2012/10/05. 10.1038/ajg.2012.93 .
    1. Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux JJ, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008;105(43):16731–6. 10.1073/pnas.0804812105

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