Alternative therapeutic applications used in the treatment of ulcerative colitis: probiotics, prebiotics, synbiotics and fecal microbiota transplantation

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Mehmet Çavdar
Meliha Çavdar


Ulcerative colitis, Inflammatory bowel disease, Probiotic, Prebiotic, Synbiotic, Fecal Microbiota Transplantation


Background: Recently, some new generation therapeutic applications that can be used as an alternative to routine pharmacological agents in the treatment of ulcerative colitis (UC) have emerged. These applications are using of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation. Objective: In this review, these therapeutic applications, which have the potential to be used as an alternative to pharmacological agents in the treatment of UC will be investigated. Results: Probiotic supplements are aimed increasing the number of beneficial bacteria in the intestinal microbiota composition, prebiotic supplements support the development of probiotics, and synbiotic supplements combine the positive metabolic effects of both prebiotic and probiotic supplements. Fecal microbiota transplantation (FMT) is used to correct dysbiosis in UC. In studies in the literature, we observed that all these applications generally mediate the improvement of the clinical remission levels of patients with UC, strengthening of the intestinal barrier mechanism, changing of the metabolic parameters of the inflammation picture positively, and the attainment of a healthier composition of the intestinal microflora. Conclusions: Alternative therapeutic applications used in the treatment of UC have been shown to have positive metabolic results on the clinical course of the disease. However, because there is no scientific consensus on the form, duration and content of such applications, further comprehensive studies should be conducted on the subject. Thus, the potential of using probiotic, prebiotic, synbiotic supplements and FMT as an alternative therapeutic application in the treatment of UC will be revealed more clearly.

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1. Langan RC, Gotsch PB, Krafczyk MA, Skillinge DD. Ulcerative Colitis: Diagnosis and Treatment. Am Fam Physician 2007; 76 (9): 1323-30.
2. Chae JM, Chang MH, Heo W, Cho HT, Lee DH, Hwang BB, Kim JW, Yoon SM, Yang S, Lee JH, Kim YJ. LB-9, Novel Probiotic Lactic Acid Bacteria, Ameliorates Dextran Sodium Sulfate-Induced Colitis in Mice by Inhibiting TNF-a-Mediated Apoptosis of Intestinal Epithelial Cells. J Med Food 2019; 22 (3): 271-6.
3. Global Cancer Observatory. (2022). Cancer Today. Accessed September 21, 2022.
4. Zhou Q, Shen ZF, Wu B, Xu C, He Z, Chen T, Shang H, Xie C, Huang S, Chen Y, Chen H, Han S. Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract 2019; 2019: 5363261.
5. Reddavide R, Rotolo O, Caruso MG, Stasi E, Notarnicola M, Miraglia C, Nouvenne A, Meschi T, Angelis GL, Mario FD, Leandro G. The role of diet in the prevention and treatment of Inflammatory Bowel Diseases. Acta Biomed 2018; 89 (9): 60-75.
6. Ramos GP, Papadakis KA. Mechanisms of Disease: Inflammatory Bowel Diseases. Mayo Clin Proc 2019; 94(1): 155–65.
7. Håkansson Å, Tormo-Badia N, Baridi A, Xu J, Molin G, Hagslätt ML, Karlsson C, Jeppsson B, Cilio CM, Ahrné S. Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice. Clin Exp Med 2015;15: 107–20.
8. Wang C, Li1 W, Wang H, Ma Y, Zhao X, Zhang X, Yang H, Qian J, Li J. Saccharomyces boulardii alleviates ulcerative colitis carcinogenesis in mice by reducing TNF-α and IL-6 levels and functions and by rebalancing intestinal microbiota. BMC Microbiol 2019; 19: 246.
9. Li B, Du P, Du Y, Zhao D, Cai Y, Yang Q, Guo Z. Luteolin alleviates inflammation and modulates gut microbiota in ulcerative colitis rats. Life Sci 2021; 269: 119008.
10. Hu Y, Ye Z, Wu M, She Y, Li L, Xu Y, Qin K, Hu Z, Yang M, Lu F, Ye Q. The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies. Front Med 2021; 8: 1-29.
11. van der Post S, Jabbar KS, Birchenough G, Arike L, Akhtar N, Sjovall H, Johansson MEV, Hansson GC. Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis. Gut 2019; 68:2142–51.
12. Yao D, Dong M, Dai C, Wu S. Inflammation and Inflammatory Cytokine Contribute to the Initiation and Development of Ulcerative Colitis and Its Associated Cancer. Inflamm Bowel Dis 2019; 25:1595-1602.
13. Shen Z, Zhu C, Quan Y, Yang Z, Wu S, Luo W, Tan B, Wang X. Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation. World J Gastroenterol 2018; 24(1): 5-14.
14. Khan I, Ullah N, Zha L, Bai Y, Khan A, Zhao T, Che T, Zhang C. Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome. Pathogens 2019; 8: 1-28.
15. Ohkusa T, Koido S. Intestinal microbiota and ulcerative colitis. J Infect Chemother 2015; 21(11): 761-68.
16. Hernández-Chirlaque C, J. Aranda C, Ocón B, Capitán-Cañadas F, Ortega-González M, Carrero JJ, Suárez MD, Zarzuelo A, de Medina FS, Martínez-Augustina O. Germ-free and Antibiotic-treated Mice are Highly Susceptible to Epithelial Injury in DSS Colitis. J Crohns Colitis 2016; 10(11): 1324-35.
17. Zou J, Liu C, Jiang S, Qian D, Duana J. Cross Talk between Gut Microbiota and Intestinal Mucosal Immunity in the Development of Ulcerative Colitis. Infect Immun 2021; 89(9): 1-16.
18. Dordević D, Jančíková S, Vítězová M, Kushkevych I. Hydrogen sulfide toxicity in the gut environment: Meta-analysis of sulfate-reducing and lactic acid bacteria in inflammatory processes. J Adv Res 2021; 27: 55-69.
19. Zakerska‐Banaszak O, Tomczak H, Gabryel M, Baturo A, Wolko L, Michalak M, Malinska N, Mankowska‐Wierzbicka D, Eder P, Dobrowolska A, Slomski R, Skrzypczak‐Zielinska M. Dysbiosis of gut microbiota in Polish patients with ulcerative colitis: a pilot study. Sci Rep 2021; 11(1): 2166.
20. Jakubczyk D, Leszczyńska K, Górska S. The Effectiveness of Probiotics in the Treatment of Inflammatory Bowel Disease (IBD)-A Critical Review. Nutrients 2020; 12(7): 1973.
21. Glassner KL, Abraham BP, Quigley EMM. The microbiome and inflammatory bowel disease. J Allergy Clin Immunol 2020; 145(1): 16-27.
22. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol 2014; 11(8): 506-514.
23. Orel R, Trop TK. Intestinal microbiota, probiotics and prebiotics in inflammatory bowel disease. World J Gastroenterol 2014; 20(33): 11505-524.
24. Derikx LAAP, Dieleman LA, Hoentjen F. Probiotics and prebiotics in ulcerative colitis. Best Pract Res Clin Gastroenterol 2016; 30(1): 55-71.
25. Dang X, Xu M, Liu D, Zhou D, Yang W. Assessing the efficacy and safety of fecal microbiota transplantation and probiotic VSL#3 for active ulcerative colitis: A systematic review and meta-analysis. PloS One 2020;15(3): e0228846.
26. Kaur L, Gordon M, Baines PA, Iheozor-Ejiofor Z, Sinopoulou V, Akobeng AK. Probiotics for induction of remission in ulcerative colitis. Cochrane Database Syst Rev 2020; 3(3): CD005573.
27. Chen P, Xu H, Tang H, Zhao F, Yang C, Kwok L, Cong C, Wu Y, Zhang W, Zhou X, Zhang H. Modulation of gut mucosal microbiota as a mechanism of probiotics-based adjunctive therapy for ulcerative colitis. Microb Biotechnol 2020; 13(6): 2032-43.
28. Iheozor-Ejiofor Z, Kaur L, Gordon M, Baines PA, Sinopoulou V, Akobeng AK. Probiotics for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 2020; 3: CD007443.
29. Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, Scott K, Stanton C, Swanson KS, Cani PD, Verbeke K, Reid G. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol 2017; 14: 491-502.
30. Laurell A, Sjöberg K. Prebiotics and synbiotics in ulcerative colitis. Scand J Gastroenterol 2017; 52(4): 477-85.
31. Maioli TU, Trindade LM, Souza A, Torres L, Andrade MER, CardosoVN, Generoso SV. Non-pharmacologic strategies for the management of intestinal inflammation. Biomed Pharmacother 2022; 145: 112414.
32. Kang S, You HJ, Ju Y, Jeong YJ, Johnston TV, Ji GE, Ku S, Park MS. Butyl-fructooligosaccharides modulate gut microbiota in healthy mice and ameliorate ulcerative colitis in a DSS-induced model. Food Funct 2022; 13(4): 1834-45.
33. Liu Z, Liu F, Wang W, Sun C, Gao D, Ma J, Hussain MA, Xu C, Jiang Z, Hou J. Study of the alleviation effects of a combination of Lactobacillus rhamnosus and inulin on mice with colitis. Food Funct 2020; 11(5): 3823-37.
34. Wang J, Zhang C, Guo C, Li X. Chitosan ameliorates DSS-induced ulcerative colitis mice by enhancing intestinal barrier function and improving microflora. Int J Mol Sci 2019; 20(22): 5751.
35. Wu M, Li P, An Y, Ren J, Yan D, Cui J, Li D, Li M, Wang M, Zhong G. Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota. Pharmacol Res 2019; 150: 104489.
36. Wilson B, Eyice Ö, Koumoutsos I, C. Lomer M, M. Irving P, O. Lindsay J, Whelan K. Prebiotic Galactooligosaccharide Supplementation in Adults with Ulcerative Colitis: Exploring the Impact on Peripheral Blood Gene Expression, Gut Microbiota, and Clinical Symptoms. Nutrients 2021; 13(10): 3598.
37. Zhang X, Guan X, Tang Y, Sun J, Wang X, Wang W, Fan J. Clinical effects and gut microbiota changes of using probiotics, prebiotics or synbiotics in inflammatory bowel disease: a systematic review and meta‐analysis. Eur J Nutr 2021; 60(5): 2855-75.
38. Martyniak A, Medyńska-Przęczek A, Wędrychowicz A, Skoczeń S, Tomasik PJ. Prebiotics, Probiotics, Synbiotics, Paraprobiotics and Postbiotic Compounds in IBD. Biomolecules 2021; 11(12): 1903.
39. Rufino NM, da Costa AL, Jorge EN, Paiano VF, Camparoto ML, Keller R, Bremer-Neto H. Synbiotics improve clinical indicators of ulcerative colitis: systematic review with meta-analysis. Nutr Rev 2022; 80(2): 157-64.
40. Wong WY, Chan BD, Leung TW, Chen MX, Tai WCS. Beneficial and anti-inflammatory effects of formulated prebiotics, probiotics, and synbiotics in normal and acute colitis mice. J Funct Foods 2022; 88: 104871.
41. Son SJ, Koh JH, Park MR, Ryu S, Lee WJ, Yun B, Lee JH, Oh S, Kim Y. Effect of the Lactobacillus rhamnosus strain GG and tagatose as a synbiotic combination in a dextran sulfate sodium-induced colitis murine model. J Dairy Sci 2019; 102: 2844-53.
42. Popov J, Caputi V, Nandeesha N, Rodriguez DA, Pai N. Microbiota-Immune Interactions in Ulcerative Colitis and Colitis Associated Cancer and Emerging Microbiota-Based Therapies. Int J Mol Sci 2021; 22: 11365.
43. Sood A, Singh A, Midha V, Mahajan R, Kao D, David T., Rubin D, Charles N, Bernstein C. Fecal Microbiota Transplantation for Ulcerative Colitis: An Evolving Therapy. Crohn’s Colitis 360 2020; 2(4): 1-7.
44. Shi Y, Dong Y, Huang W, Zhu D, Mao H, Su P. Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis. PLoS One 2016; 11(6): e0157259.
45. Moayyedi P, Surette MG, Kim PT, Libertucci J, Wolfe M, Onischi C, Armstrong D, Marshall JK, Kassam Z, Reinisch W, Lee CH. Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology 2015; 149(1): 102-9.
46. Kunde S, Pham A, Bonczyk S, Crumb T, Duba M, Conrad Jr H, Cloney D, Kugathasan S. Safety, Tolerability, and Clinical Response After Fecal Transplantation in Children and Young Adults With Ulcerative Colitis. J Pediatr Gastroenterol Nutr 2013; 56(6): 597–601.
47. Paramsothy S, Kamm MA, Kaakoush NO, Walsh AJ, van den Bogaerde J, Samuel D, Leong RWL, Connor S, Ng W, Paramsothy R, Xuan W, Lin E, Mitchell HM, Borody TJ. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet 2017; 389(10075): 1218–28.
48. Costello SP, Hughes PA, Waters O, Bryant RV, Vincent AD, Blatchford P, Katsikeros R, Makanyanga J, Campaniello MA, Mavrangelos C, Rosewarne CP, Bickley C, Peters C, Schoeman MN, Conlon MA, Roberts-Thomson IC, Andrews JM. Effect of fecal microbiota transplantation on 8-week remission in patients with ulcerative colitis: a randomized clinical trial. JAMA 2019; 321(2): 156-64.
49. Caldeira LdF, Borba HH, Tonin FS, Wiens A, Fernandez-Llimos F, Pontarolo R. Fecal microbiota transplantation in inflammatory bowel disease patients: A systematic review and meta-analysis. PLoS One 2020; 15(9): e0238910.
50. Rossen NG, Fuentes S, van der Spek MJ, Tijssen JG, Hartman JHA, Duflou A, Löwenberg M, van den Brink GR, Mathus-Vliegen EMH, de Vos WM, Zoetendal EG, D’Haens GR, Ponsioen CY. Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. Gastroenterology 2015; 149(1): 110-18.
51. Guo XY, Liu XJ, Hao JY. Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment. J Dig Dis 2020; 21(3): 147-59.