BACKGROUND AND AIMS: Ulcerative colitis (UC) is a chronic inflammatory disease. Fecal microbial transplantation (FMT) is a promising alternative treatment. METHODS: This multicenter, open-label, noninferiority trial randomized patients with active left-sided UC (Mayo score 4-10) equally to FMT or 5-aminosalicylic acid (5-ASA) enemas. FMT enemas were administered five times in the first week and then once weekly for 5 weeks. 5-ASA enemas were administered daily for 2 weeks and then every other day. The primary study endpoint was clinical remission, with a total Mayo score ≤2 at week 12 with no subscore >1. RESULTS: Sixty-one patients were screened; 45 were enrolled and randomized to FMT (n = 23) or 5-ASA (n = 22). Twenty-one FMT and 22 5-ASA patients completed at least the week 4 study visit and were included in the mITT analysis. Twelve FMT (57%) and eight 5-ASA patients achieved the primary study endpoint. FMT noninferiority with 10% margin was confirmed (95% CI: -7.6%, 48.9%). Adverse events occurred in 12 FMT (57%) and 13 5-ASA (59%) patients. Increased microbial diversity persisted 3 months after FMT. CONCLUSION: FMT is an effective treatment for left-sided UC and increased recipient microbiome diversity. Targeted microbiome modification may improve FMT efficacy. Further investigation is needed to guide donor and patient selection.

4th Department of Medicine Department of Gastroenterology and Hepatology 1st Faculty of Medicine Charles University and General University Hospital Prague 12808 Prague Czech Republic

Clinical and Research Centre for IBD ISCARE 19000 Prague Czech Republic

Gastroenterology Department 1 Internal Clinic University Hospital in Pilsen 30100 Pilsen Czech Republic

Hepatogastroenterology Department Institute for Clinical and Experimental Medicine 14021 Prague Czech Republic

Institute of Animal Physiology and Genetics of the Czech Academy of Science v v i 14220 Prague Czech Republic

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Lloyd-Price J., Arze C., Ananthakrishnan A.N., Schirmer M., Avila-Pacheco J., Poon T.W., Andrews E., Ajami N.J., Bonham K.S., Brislawn C.J., et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature. 2019;569:655–662. doi: 10.1038/s41586-019-1237-9. PubMed DOI PMC

Duvallet C., Gibbons S.M., Gurry T., Irizarry R.A., Alm E.J. Meta-analysis of gut microbiome studies identifies disease-specific and shared responses. Nat. Commun. 2017;8:1784. doi: 10.1038/s41467-017-01973-8. PubMed DOI PMC

Kaur L., Gordon M., Baines P.A., Iheozor-Ejiofor Z., Sinopoulou V., Akobeng A.K. Probiotics for induction of remission in ulcerative colitis. Cochrane Database Syst. Rev. 2020;3:CD005573. doi: 10.1002/14651858.CD005573.pub3. PubMed DOI PMC

Laurell A., Sjoberg K. Prebiotics and synbiotics in ulcerative colitis. Scand. J. Gastroenterol. 2017;52:477–485. doi: 10.1080/00365521.2016.1263680. PubMed DOI

Van Nood E., Vrieze A., Nieuwdorp M., Fuentes S., Zoetendal E.G., de Vos W.M., Visser C.E., Kuijper E.J., Bartelsman J.F., Tijssen J.G., et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 2013;368:407–415. doi: 10.1056/NEJMoa1205037. PubMed DOI

Quraishi M.N., Widlak M., Bhala N., Moore D., Price M., Sharma N., Iqbal T.H. Systematic review with meta-analysis: The efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection. Aliment. Pharmacol. Ther. 2017;46:479–493. doi: 10.1111/apt.14201. PubMed DOI

Moayyedi P., Surette M.G., Kim P.T., Libertucci J., Wolfe M., Onischi C., Armstrong D., Marshall J.K., Kassam Z., Reinisch W., et al. Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology. 2015;149:102–109.e6. doi: 10.1053/j.gastro.2015.04.001. PubMed DOI

Rossen N.G., Fuentes S., van der Spek M.J., Tijssen J.G., Hartman J.H., Duflou A., Lowenberg M., van den Brink G.R., Mathus-Vliegen E.M., de Vos W.M., et al. Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. Gastroenterology. 2015;149:110–118.e4. doi: 10.1053/j.gastro.2015.03.045. PubMed DOI

Paramsothy S., Kamm M.A., Kaakoush N.O., Walsh A.J., van den Bogaerde J., Samuel D., Leong R.W.L., Connor S., Ng W., Paramsothy R., et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: A randomised placebo-controlled trial. Lancet. 2017;389:1218–1228. doi: 10.1016/S0140-6736(17)30182-4. PubMed DOI

Costello S.P., Hughes P.A., Waters O., Bryant R.V., Vincent A.D., Blatchford P., Katsikeros R., Makanyanga J., Campaniello M.A., Mavrangelos C., et al. Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial. JAMA. 2019;321:156–164. doi: 10.1001/jama.2018.20046. PubMed DOI PMC

Sood A., Mahajan R., Singh A., Midha V., Mehta V., Narang V., Singh T., Singh Pannu A. Role of Faecal Microbiota Transplantation for Maintenance of Remission in Patients With Ulcerative Colitis: A Pilot Study. J. Crohns Colitis. 2019;13:1311–1317. doi: 10.1093/ecco-jcc/jjz060. PubMed DOI

Da Silva B.C., Lyra A.C., Rocha R., Santana G.O. Epidemiology, demographic characteristics and prognostic predictors of ulcerative colitis. World J. Gastroenterol. 2014;20:9458–9467. doi: 10.3748/wjg.v20.i28.9458. PubMed DOI PMC

Cohen R.D., Woseth D.M., Thisted R.A., Hanauer S.B. A meta-analysis and overview of the literature on treatment options for left-sided ulcerative colitis and ulcerative proctitis. Am. J. Gastroenterol. 2000;95:1263–1276. doi: 10.1111/j.1572-0241.2000.01940.x. PubMed DOI

Fliegerova K., Tapio I., Bonin A., Mrazek J., Callegari M.L., Bani P., Bayat A., Vilkki J., Kopecny J., Shingfield K.J., et al. Effect of DNA extraction and sample preservation method on rumen bacterial population. Anaerobe. 2014;29:80–84. doi: 10.1016/j.anaerobe.2013.09.015. PubMed DOI

Bolyen E., Rideout J.R., Dillon M.R., Bokulich N.A., Abnet C.C., Al-Ghalith G.A., Alexander H., Alm E.J., Arumugam M., Asnicar F., et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat. Biotechnol. 2019;37:852–857. doi: 10.1038/s41587-019-0209-9. PubMed DOI PMC

Callahan B.J., McMurdie P.J., Rosen M.J., Han A.W., Johnson A.J., Holmes S.P. DADA2: High-resolution sample inference from Illumina amplicon data. Nat. Methods. 2016;13:581–583. doi: 10.1038/nmeth.3869. PubMed DOI PMC

Rognes T., Flouri T., Nichols B., Quince C., Mahe F. VSEARCH: A versatile open source tool for metagenomics. PeerJ. 2016;4:e2584. doi: 10.7717/peerj.2584. PubMed DOI PMC

Segata N., Izard J., Waldron L., Gevers D., Miropolsky L., Garrett W.S., Huttenhower C. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12:R60. doi: 10.1186/gb-2011-12-6-r60. PubMed DOI PMC

Biancone L., Gionchetti P., Blanco Gdel V., Orlando A., Annese V., Papi C., Sostegni R., D’Inca R., Petruzziello C., Casa A., et al. Beclomethasone dipropionate versus mesalazine in distal ulcerative colitis: A multicenter, randomized, double-blind study. Dig. Liver Dis. 2007;39:329–337. doi: 10.1016/j.dld.2007.01.012. PubMed DOI

Anderson J.L., Edney R.J., Whelan K. Systematic review: Faecal microbiota transplantation in the management of inflammatory bowel disease. Aliment. Pharmacol. Ther. 2012;36:503–516. doi: 10.1111/j.1365-2036.2012.05220.x. PubMed DOI

Rajilic-Stojanovic M., Shanahan F., Guarner F., de Vos W.M. Phylogenetic analysis of dysbiosis in ulcerative colitis during remission. Inflamm. Bowel Dis. 2013;19:481–488. doi: 10.1097/MIB.0b013e31827fec6d. PubMed DOI

Kassam Z., Hundal R., Marshall J.K., Lee C.H. Fecal transplant via retention enema for refractory or recurrent Clostridium difficile infection. Arch. Intern. Med. 2012;172:191–193. doi: 10.1001/archinte.172.2.191. PubMed DOI

Shen Z.H., Zhu C.X., Quan Y.S., Yang Z.Y., Wu S., Luo W.W., Tan B., Wang X.Y. Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation. World J. Gastroenterol. 2018;24:5–14. doi: 10.3748/wjg.v24.i1.5. PubMed DOI PMC

Xu J., Chen N., Wu Z., Song Y., Zhang Y., Wu N., Zhang F., Ren X., Liu Y. 5-Aminosalicylic Acid Alters the Gut Bacterial Microbiota in Patients With Ulcerative Colitis. Front. Microbiol. 2018;9:1274. doi: 10.3389/fmicb.2018.01274. PubMed DOI PMC

Khanna S., Raffals L.E. The Microbiome in Crohn’s Disease: Role in Pathogenesis and Role of Microbiome Replacement Therapies. Gastroenterol. Clin. N. Am. 2017;46:481–492. doi: 10.1016/j.gtc.2017.05.004. PubMed DOI

Schierova D., Brezina J., Mrazek J., Fliegerova K.O., Kvasnova S., Bajer L., Drastich P. Gut Microbiome Changes in Patients with Active Left-Sided Ulcerative Colitis after Fecal Microbiome Transplantation and Topical 5-aminosalicylic Acid Therapy. Cells. 2020;9:2283. doi: 10.3390/cells9102283. PubMed DOI PMC

Chen H.T., Huang H.L., Xu H.M., Luo Q.L., He J., Li Y.Q., Zhou Y.L., Nie Y.Q., Zhou Y.J. Fecal microbiota transplantation ameliorates active ulcerative colitis. Exp. Ther. Med. 2020;19:2650–2660. doi: 10.3892/etm.2020.8512. PubMed DOI PMC

Sokol H., Landman C., Seksik P., Berard L., Montil M., Nion-Larmurier I., Bourrier A., Le Gall G., Lalande V., De Rougemont A., et al. Fecal microbiota transplantation to maintain remission in Crohn’s disease: A pilot randomized controlled study. Microbiome. 2020;8:12. doi: 10.1186/s40168-020-0792-5. PubMed DOI PMC

Olaisen M., Spigset O., Flatberg A., Granlund A.V.B., Brede W.R., Albrektsen G., Royset E.S., Gilde B., Sandvik A.K., Martinsen T.C., et al. Mucosal 5-aminosalicylic acid concentration, drug formulation and mucosal microbiome in patients with quiescent ulcerative colitis. Aliment. Pharmacol. Ther. 2019;49:1301–1313. doi: 10.1111/apt.15227. PubMed DOI PMC

Jalanka J., Hillamaa A., Satokari R., Mattila E., Anttila V.J., Arkkila P. The long-term effects of faecal microbiota transplantation for gastrointestinal symptoms and general health in patients with recurrent Clostridium difficile infection. Aliment. Pharmacol. Ther. 2018;47:371–379. doi: 10.1111/apt.14443. PubMed DOI

Goloshchapov O.V., Olekhnovich E.I., Sidorenko S.V., Moiseev I.S., Kucher M.A., Fedorov D.E., Pavlenko A.V., Manolov A.I., Gostev V.V., Veselovsky V.A., et al. Long-term impact of fecal transplantation in healthy volunteers. BMC Microbiol. 2019;19:312. doi: 10.1186/s12866-019-1689-y. PubMed DOI PMC