Crohn’s disease (CD) is a chronic inflammatory disease whose pathogenesis involves disturbances of the gastrointestinal microbiota. As the prevalence of CD increases, the need for a more effective and safe treatment is integral. Probiotics have been reported to be beneficial for numerous gastrointestinal diseases, providing health benefits and considering the microbial characteristics of CD’s pathogenesis. However, our knowledge of the efficacy of probiotic therapy in preventing relapse in CD is limited. How gastroenterologists have incorporated probiotics into their practice or probiotics observed implications for patients with CD has not been assessed. A quantitative survey was distributed to determine how gastroenterologists perceive and use probiotic-based therapies in CD practice. The second objective was to conduct a meta-analysis of the efficacy of probiotics for maintaining remission and preventing clinical and endoscopic relapse in CD. Performing a meta-analysis and survey will examine the role of probiotics in CD treatment. Surveyed gastroenterologists cited that probiotics have an adjunctive role and have been observed to alleviate common CD symptoms. Probiotics seem effective in reducing the relapse rate, specifically those of the multi-strain variety are more likely to be effective in maintaining CD remission. Further research with larger trials is required to replicate and solidify this efficacy. The meta-analysis only assessed the efficacy of probiotics as a maintenance treatment as measured by the risk of relapse; thus, no evidence supports probiotics’ ability to induce remission. The results of the meta-analysis and survey indicate that probiotics cannot treat CD without accompanying conventional drug therapies; nevertheless, independent of treatment capacities, probiotics still yield health benefits for CD patients.
References
[1]
Peña-Sánchez, J.N., Osei, J.A., Marques Santos, J.D., Jennings, D., Andkhoie, M., Brass, C., Bukassa-Kazadi, G., Lu, X., Johnson-Jennings, M., Porter, L., Porter, R., Quintin, C.L., Sanderson, R., Teucher, U. and Fowler, S. (2022) Increasing Prevalence and Stable Incidence Rates of Inflammatory Bowel Disease among First Nations: Population-Based Evidence from a Western Canadian Province. Inflammatory Bowel Diseases, 28, 514-522. https://doi.org/10.1093/ibd/izab096
[2]
Fava, F. and Danese, S. (2011) Intestinal Microbiota in Inflammatory Bowel Disease: Friend of Foe? World Journal of Gastroenterology, 17, 557-566. https://doi.org/10.3748/wjg.v17.i5.557
[3]
McFall-Ngai M. (2007) Adaptive Immunity: Care for the Community. Nature, 445, 153. https://doi.org/10.1038/445153a
[4]
Lémann, M. (2006) Review Article: Can Post-Operative Recurrence in Crohn’s Disease Be Prevented? Alimentary Pharmacology & Therapeutics, 24, 22-28. https://doi.org/10.1111/j.1365-2036.2006.03055.x
[5]
Colombel, J.F., Sandborn, W.J., Reinisch, W., Mantzaris, G.J., Kornbluth, A., Rachmilewitz, D., Lichtiger, S., D’Haens, G., Diamond, R.H., Broussard, D.L., Tang, K.L., van der Woude, C.J., Rutgeerts, P. and SONIC Study Group (2010) Infliximab, Azathioprine, or Combination Therapy for Crohn’s Disease. The New England Journal of Medicine, 362, 1383-1395. https://doi.org/10.1056/NEJMoa0904492
[6]
Wilkins, T., Jarvis, K. and Patel, J. (2011) Diagnosis and Management of Crohn’s Disease. American Family Physician, 84, 1365-1375.
[7]
Ciorba, M.A. (2012) A Gastroenterologist’s Guide to Probiotics. Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association, 10, 960-968. https://doi.org/10.1016/j.cgh.2012.03.024
[8]
Cristofori, F., Dargenio, V.N., Dargenio, C., Miniello, V.L., Barone, M. and Francavilla, R. (2021) Anti-Inflammatory and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body. Frontiers in Immunology, 12, Article ID: 578386. https://doi.org/10.3389/fimmu.2021.578386
[9]
Tamboli, C.P., Neut, C., Desreumaux, P. and Colombel, J.F. (2004) Dysbiosis in Inflammatory Bowel Disease. Gut, 53, 1-4. https://doi.org/10.1136/gut.53.1.1
[10]
Sartor, R.B. (2004) Therapeutic Manipulation of the Enteric Microflora in Inflammatory Bowel Diseases: Antibiotics, Probiotics, and Prebiotics. Gastroenterology, 126, 1620-1633. https://doi.org/10.1053/j.gastro.2004.03.024
[11]
Fedorak, R.N. and Madsen, K.L. (2004) Probiotics and the Management of Inflammatory Bowel Disease. Inflammatory Bowel Diseases, 10, 286-299. https://doi.org/10.1097/00054725-200405000-00018
[12]
Shibolet, O., Karmeli, F., Eliakim, R., Swennen, E., Brigidi, P., Gionchetti, P., Campieri, M., Morgenstern, S. and Rachmilewitz, D. (2002) Variable Response to Probiotics in Two Models of Experimental Colitis in Rats. Inflammatory Bowel Diseases, 8, 399-406. https://doi.org/10.1097/00054725-200211000-00004
[13]
McCarthy, J., O’Mahony, L., O’Callaghan, L., Sheil, B., Vaughan, E.E., Fitzsimons, N., Fitzgibbon, J., O’Sullivan, G.C., Kiely, B., Collins, J.K. and Shanahan, F. (2003) Double Blind, Placebo Controlled Trial of Two Probiotic Strains in Interleukin 10 Knockout Mice and Mechanistic Link with Cytokine Balance. Gut, 52, 975-980. https://doi.org/10.1136/gut.52.7.975
[14]
Madsen, K., Cornish, A., Soper, P., McKaigney, C., Jijon, H., Yachimec, C., Doyle, J., Jewell, L. and De Simone, C. (2001) Probiotic Bacteria Enhance Murine and Human Intestinal Epithelial Barrier Function. Gastroenterology, 121, 580-591. https://doi.org/10.1053/gast.2001.27224
[15]
Kaur, L., Gordon, M., Baines, P.A., Iheozor-ejiofor, Z., Sinopoulou, V. and Akobeng, A.K. (2020) Probiotics for Induction of Remission in Ulcerative Colitis. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.CD005573.pub3
[16]
Iheozor-ejiofor, Z., Kaur, L., Gordon, M., Baines, P.A., Sinopoulou, V. and Akobeng, A.K. (2020) Probiotics for Maintenance of Remission in Ulcerative Colitis. Cochrane Database of Systematic Reviews, 3, CD005573. https://doi.org/10.1002/14651858.CD007443.pub3
[17]
Nguyen, N., Zhang, B., Holubar, S.D., Pardi, D.S. and Singh, S. (2019) Treatment and Prevention of Pouchitis after Ileal Pouch-Anal Anastomosis for Chronic Ulcerative Colitis. Cochrane Database of Systematic Reviews, 5, CD001176. https://doi.org/10.1002/14651858.CD001176.pub5
[18]
Rolfe, V.E., Fortun, P.J., Hawkey, C.J. and Bath-Hextall, F. (2006) Probiotics for Maintenance of Remission in Crohn’s Disease. The Cochrane Database of Systematic Reviews, 4, CD004826. https://doi.org/10.1002/14651858.CD004826.pub2
[19]
Su, G.L., Ko, C.W., Bercik, P., Falck-ytter, Y., Sultan, S., Weizman, A.V. and Morgan, R.L. (2020) AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders. Gastroenterology, 159, 697-705. https://doi.org/10.1053/j.gastro.2020.05.059
[20]
Williams, M.D., Ha, C.Y. and Ciorba, M.A. (2010) Probiotics as Therapy in Gastroenterology: A Study of Physician Opinions and Recommendations. Journal of Clinical Gastroenterology, 44, 631-636. https://doi.org/10.1097/MCG.0b013e3181d47f5b
[21]
Kerry, R.G. et al. (2018) Probiotics: The Ultimate Nutritional Supplement. In: Patra, J., Das, G. and Shin, H.S., Eds., Microbial Biotechnology, Springer, Singapore, 141-152. https://doi.org/10.1007/978-981-10-7140-9_7
[22]
Best, W.R., Becktel, J.M., Singleton, J.W. and Kern, F., Jr (1976) Development of a Crohn’s Disease Activity Index. National Cooperative Crohn’s Disease Study. Gastroenterology, 70, 439-444. https://doi.org/10.1016/S0016-5085(76)80163-1
[23]
Townsend, C.M., Parker, C.E., MacDonald, J.K., Nguyen, T.M., Jairath, V., Feagan, B.G. and Khanna, R. (2019) Antibiotics for Induction and Maintenance of Remission in Crohn’s Disease. The Cochrane Database of Systematic Reviews, 2, CD012730. https://doi.org/10.1002/14651858.CD012730.pub2
[24]
Moher, D., Cook, D.J., Eastwood, S., Olkin, I., Rennie, D. and Stroup, D.F. (2000) Improving the Quality of Reports of Meta-Analyses of Randomised Controlled Trials: The QUOROM Statement. British Journal of Surgery, 87, 1448-1454. https://doi.org/10.1159/000055014
[25]
Rahimi, R., Nikfar, S., Rahimi, F., Elahi, B., Derakhshani, S., Vafaie, M. and Abdollahi, M. (2008) A Meta-Analysis on the Efficacy of Probiotics for Maintenance of Remission and Prevention of Clinical and Endoscopic Relapse in Crohn’s Disease. Digestive Diseases and Sciences, 53, 2524-2531. https://doi.org/10.1007/s10620-007-0171-0
[26]
Limketkai, B.N., Akobeng, A.K., Gordon, M. and Adepoju, A.A. (2020) Probiotics for Induction of Remission in Crohn’s Disease. Cochrane Database of Systematic Reviews, 7, CD006634. https://doi.org/10.1002/14651858.CD006634.pub3
[27]
Higgins, J.P., Thompson, S.G., Deeks, J.J. and Altman, D.G. (2003) Measuring Inconsistency in Meta-Analyses. BMJ (Clinical Research ed.), 327, 557-560. https://doi.org/10.1136/bmj.327.7414.557
[28]
Malchow, H.A. (1997) Crohn’s Disease and Escherichia coli. A New Approach in Therapy to Maintain Remission of Colonic Crohn’s Disease? Journal of Clinical Gastroenterology, 25, 653-658. https://doi.org/10.1097/00004836-199712000-00021
[29]
Prantera, C., Scribano, M.L., Falasco, G., Andreoli, A. and Luzi, C. (2002) Ineffectiveness of Probiotics in Preventing Recurrence after Curative Resection for Crohn’s Disease: A Randomised Controlled Trial with Lactobacillus GG. Gut, 51, 405-409. https://doi.org/10.1136/gut.51.3.405
[30]
Schultz, M., Timmer, A., Herfarth, H.H., Sartor, R.B., Vanderhoof, J.A. and Rath, H.C. (2004) Lactobacillus GG in Inducing and Maintaining Remission of Crohn’s Disease. BMC Gastroenterology, 4, Article No. 5. https://doi.org/10.1186/1471-230X-4-5
[31]
Zocco, M.A., dal Verme, L.Z., Cremonini, F., Piscaglia, A.C., Nista, E.C., Candelli, M., Novi, M., Rigante, D., Cazzato, I.A., Ojetti, V., Armuzzi, A., Gasbarrini, G. and Gasbarrini, A. (2006) Efficacy of Lactobacillus GG in Maintaining Remission of Ulcerative Colitis. Alimentary Pharmacology & Therapeutics, 23, 1567-1574. https://doi.org/10.1111/j.1365-2036.2006.02927.x
[32]
Guslandi, M., Mezzi, G., Sorghi, M. and Testoni, P.A. (2000) Saccharomyces boulardii in Maintenance Treatment of Crohn’s Disease. Digestive Diseases and Sciences, 45, 1462-1464. https://doi.org/10.1023/A:1005588911207
[33]
Bourreille, A., Cadiot, G., Le Dreau, G., Laharie, D., Beaugerie, L., Dupas, J.L., Marteau, P., Rampal, P., Moyse, D., Saleh, A., Le Guern, M.E., Galmiche, J.P. and FLORABEST Study Group (2013) Saccharomyces boulardii Does Not Prevent Relapse of Crohn’s Disease. Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association, 11, 982-987. https://doi.org/10.1016/j.cgh.2013.02.021
[34]
Desreumaux, P., Dewit, O., Belaiche, J., Savoye, G., Dupas, J.-L., Lemann, M., Bouhnik, Y., Grimaud, J.-C., Casellas, F., Panes, J., Bigard, M.-A., De vos, M., Carbonnel, F., Marteau, P., Vermeire, S., Bourreille, A., Gisbert, J.P., Darfeuille-Michaud, A., Tondu, F. and Colombel, J.-F. (2010) T2027 Lactobacillus casei Dn-114 Oo1 Strain in the Prevention of Postoperative Recurrence of Crohn’s Disease: A Randomised, Double-Blind Placebo-Controlled Trial. Gastroenterology, 138, S-616. https://doi.org/10.1016/S0016-5085(10)62840-5
[35]
Van Gossum, A., Dewit, O., Louis, E., de Hertogh, G., Baert, F., Fontaine, F., DeVos, M., Enslen, M., Paintin, M. and Franchimont, D. (2007) Multicenter Randomized-Controlled Clinical Trial of Probiotics (Lactobacillus johnsonii, LA1) on Early Endoscopic Recurrence of Crohn’s Disease after Lleo-Caecal Resection. Inflammatory Bowel Diseases, 13, 135-142. https://doi.org/10.1002/ibd.20063
[36]
Marteau, P., Lémann, M., Seksik, P., Laharie, D., Colombel, J.F., Bouhnik, Y., Cadiot, G., Soulé, J.C., Bourreille, A., Metman, E., Lerebours, E., Carbonnel, F., Dupas, J.L., Veyrac, M., Coffin, B., Moreau, J., Abitbol, V., Blum-Sperisen, S. and Mary, J.Y. (2006) Ineffectiveness of Lactobacillus johnsonii LA1 for Prophylaxis of Postoperative Recurrence in Crohn’s Disease: A Randomised, Double Blind, Placebo Controlled GETAID Trial. Gut, 55, 842-847. https://doi.org/10.1136/gut.2005.076604
[37]
Steed, H., Macfarlane, G.T., Blackett, K.L., Bahrami, B., Reynolds, N., Walsh, S.V., Cummings, J.H. and Macfarlane, S. (2010) Clinical Trial: The Microbiological and Immunological Effects of Synbiotic Consumption—A Randomized Double-Blind Placebo-Controlled Study in Active Crohn’s Disease. Alimentary Pharmacology & Therapeutics, 32, 872-883. https://doi.org/10.1111/j.1365-2036.2010.04417.x
[38]
Fedorak, R.N., Feagan, B.G., Hotte, N., Leddin, D., Dieleman, L.A., Petrunia, D.M., Enns, R., Bitton, A., Chiba, N., Paré, P., Rostom, A., Marshall, J., Depew, W., Bernstein, C.N., Panaccione, R., Aumais, G., Steinhart, A.H., Cockeram, A., Bailey, R.J., Gionchetti, P. and Madsen, K. (2015) The Probiotic VSL#3 Has Anti-Inflam-matory Effects and Could Reduce Endoscopic Recurrence after Surgery for Crohn’s Disease. Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association, 13, 928-935.e2. https://doi.org/10.1016/j.cgh.2014.10.031
[39]
Campieri, M., Rizzello, F., Venturi, A., Poggioli, G. and Ugolini, F. (2000) Combination of Antibiotic and Probiotic Treatment Is Efficacious in Prophylaxis of Post-Operative Recurrence of Crohn’s Disease: A Randomized Controlled Study vs Mesalamine. Gastroenterology, 118, A781. https://doi.org/10.1016/S0016-5085(00)85267-1
[40]
Higgins, J.P.T., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M.J. and Welch, V.A. (2020) Cochrane Handbook for Systematic Reviews of Interventions. 2nd Edition, Wiley-Blackwell, Hoboken. https://doi.org/10.1002/9781119536604
[41]
O’connor, L.E., Gahche, J.J., Herrick, K.A., Davis, C.D., Potischman, N. and Vargas, A.J. (2021) Nonfood Prebiotic, Probiotic, and Synbiotic Use Has Increased in US Adults and Children from 1999 to 2018. Gastroenterology, 161, 476-486.e3. https://doi.org/10.1053/j.gastro.2021.04.037
[42]
Didari, T., Mozaffari, S., Nikfar, S. and Abdollahi, M. (2015) Effectiveness of Probiotics in Irritable Bowel Syndrome: Updated Systematic Review with Meta-Analysis. World Journal of Gastroenterology, 21, 3072-3084. https://doi.org/10.3748/wjg.v21.i10.3072
[43]
Halpin, S.J. and Ford, A.C. (2012) Prevalence of Symptoms Meeting Criteria for Irritable Bowel Syndrome in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis. American Journal of Gastroenterology, 107, 1474-1482. https://doi.org/10.1038/ajg.2012.260
[44]
Scott, B.M., Gutiérrez-vázquez, C., Sanmarco, L.M., Da silva pereira, J.A., Li, Z., Plasencia, A., Hewson, P., Cox, L.M., O’brien, M., Chen, S.K., Moraes-vieira, P.M., Chang, B.S.W., Peisajovich, S.G. and Quintana, F.J. (2021) Self-Tunable Engineered Yeast Probiotics for the Treatment of Inflammatory Bowel Disease. Nature Medicine, 27, 1212-1222. https://doi.org/10.1038/s41591-021-01390-x
