Probiotics for the prevention of antibiotic-associated diarrhea – an umbrella review of meta-analyses of randomized controlled trials
DOI:
https://doi.org/10.15584/ejcem.2025.1.22Keywords:
antibiotic-associated diarrhea, Lactobacillus, probioticsAbstract
Introduction and aim. Antibiotic therapies induce diarrhea by disrupting the intestinal microbiota, prompting research into probiotics to prevent antibiotic-associated diarrhea (AAD). The aim of this study was to systematically identify and summarize meta-analyses of randomized controlled trials (RCT) on probiotics for AAD prevention.
Material and methods. Databases including PubMed, EMBASE, Epistemonikos, and the Cochrane Database were searched up to December 11, 2023. Systematic reviews and meta-analyses of RCTs on probiotics for AAD prevention in any age group were included. Meta-analyses were re-performed to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). Evidence quality was assessed using GRADE criteria.
Analysis of the literature. The review included 16 articles with 39 unique meta-analyses. Probiotics reduced AAD risk across various groups: adults (RR 0.47, 95% CI 0.40–0.56), all ages (RR 0.58, 95% CI 0.50–0.68), and outpatients (RR 0.49, 95% CI 0.36 0.66) with a moderate level of evidence. For the use of any probiotics in pediatrics, the initial high-quality evidence (RR 0.48, 95% CI 0.44–0.63) was downgraded to moderate after a sensitivity analysis excluding small studies.
Conclusion. Probiotics are beneficial in preventing AAD, but evidence quality varies from low to moderate. High-quality trials are needed to identify the most effective probiotic species and strains, dosages, and target patient populations.
Downloads
References
Högenauer C, Hammer HF, Krejs GJ, et al. Mechanisms and management of antibiotic-associated diarrhea. Clin Infect Dis. 1998;27(4):702-710. doi: 10.1086/514958
Kuehn J, Ismael Z, Long PF, et al. Reported rates of diarrhea following oral penicillin therapy in pediatric clinical trials. J Pediatr Pharmacol Ther. 2015;20(2):90-104. doi: 10.5863/1551-6776-20.2.90
McFarland LV. Antibiotic-associated diarrhea: epidemiology, trends and treatment. Future Microbiol. 2008;3(5):563-578. doi: 10.2217/17460913.3.5.563
Barbut F, Meynard JL. Managing antibiotic associated diarrhoea. BMJ. 2002;324(7350):1345-1346. doi: 10.1136/bmj.324.7350.1345
Elseviers MM, Van Camp Y, Nayaert S, et al. Prevalence and management of antibiotic associated diarrhea in general hospitals. BMC Infect Dis. 2015;15:129. doi: 10.1186/s12879-015-0869-0
Kyne L, Hamel MB, Polavaram R, et al. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. Clin Infect Dis. 2002;34(3):346-353. doi: 10.1086/338260
Dubberke ER, Reske KA, Olsen MA, et al. Short- and long-term attributable costs of Clostridium difficile-associated disease in nonsurgical inpatients. Clin Infect Dis. 2008;46(4):497-504. doi: 10.1086/526530
Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-514. doi: 10.1038/nrgastro.2014.66
Mekonnen SA, Merenstein D, Fraser CM, et al. Molecular mechanisms of probiotic prevention of antibiotic-associated diarrhea. Curr Opin Biotechnol. 2020;61:226-234. doi: 10.1016/j.copbio.2020.01.005
Capurso L. Thirty years of Lactobacillus rhamnosus GG: A review. J Clin Gastroenterol. 2019;53(1):1-41. doi: 10.1097/MCG.0000000000001170
Czerucka D, Rampal P. Diversity of Saccharomyces boulardii CNCM I-745 mechanisms of action against intestinal infections. World J Gastroenterol. 2019;25(18):2188-2203. doi: 10.3748/wjg.v25.i18.2188
Guo Q, Goldenberg JZ, Humphrey C, et al. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev. 2019;4(4):Cd004827. Doi: 10.1002/14651858.CD004827.pub5
Hempel S, Newberry SJ, Maher AR, et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: A systematic review and meta-analysis. JAMA. 2012;307(18):1959-1969. doi: 10.1001/jama.2012.3507
Goodman C, Keating G, Georgousopoulou E, et al. Probiotics for the prevention of antibiotic-associated diarrhoea: a systematic review and meta-analysis. BMJ Open. 2021;11(8):e043054. doi: 10.1136/bmjopen-2020-043054
Liao W, Chen C, Wen T, et al. Probiotics for the prevention of antibiotic-associated diarrhea in adults: A meta-Analysis of randomized placebo-controlled trials. J Clin Gastroenterol. 2021;55(6):469-480. doi: 10.1097/MCG.0000000000001464
Collinson S, Deans A, Padua-Zamora A, et al. Probiotics for treating acute infectious diarrhoea. Cochrane Database Syst Rev. 2020;12(12):Cd003048. doi: 10.1002/14651858.CD003048.pub4
Patikorn C, Roubal K, Veettil SK, et al. Intermittent fasting and obesity-related health outcomes: An umbrella review of meta-analyses of randomized clinical trials. JAMA Netw Open. 2021;4(12):e2139558. doi: 10.1001/jamanetworko-pen.2021.39558
Veettil SK, Sadoyu S, Bald EM, et al. Association of proton-pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta-analyses of cohort studies and randomised controlled trials. Br J Clin Pharmacol. 2022;88(4):1551-1566. doi: 10.1111/bcp.15103
Veettil SK, Wong TY, Loo YS, et al. Role of diet in colorectal cancer incidence: Umbrella review of meta-analyses of prospective observational studies. JAMA Netw Open. 2021;4(2):e2037341. doi: 10.1001/jamanetworkopen.2020.37341
Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71
Theodoratou E, Tzoulaki I, Zgaga L, et al. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014;348:g2035. doi: 10.1136/bmj.g2035
Dragioti E, Solmi M, Favaro A, et al. Association of antidepressant use with adverse health outcomes: A systematic umbrella review. JAMA Psychiatry. 2019;76(12):1241-1255. doi: 10.1001/jamapsychiatry.2019.2859
Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;358:j4008. doi: 10.1136/bmj.j4008
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177-188.
Higgins JP, Thompson SG, Spiegelhalter DJ. A re-evaluation of random-effects meta-analysis. J R Stat Soc Ser Stat Soc. 2009;172(1):137-159. doi: 10.1111/j.1467-985X.2008.00552.x
Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-634. doi: 10.1136/bmj.315.7109.629
Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924-926. doi: 10.1136/bmj.39489.470347.AD
Dechartres A, Altman DG, Trinquart L, et al. Association between analytic strategy and estimates of treatment outcomes in meta-analyses. JAMA. 2014;312(6):623-630. doi: 10.1001/jama.2014.8166
Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. doi: 10.1136/bmj.l4898
Agamennone V, Krul CAM, Rijkers G, et al. A practical guide for probiotics applied to the case of antibiotic-associated diarrhea in The Netherlands. BMC Gastroenterol. 2018;18(1):103. doi: 10.1186/s12876-018-0831-x
Blaabjerg S, Artzi DM, Aabenhus R. Probiotics for the prevention of antibiotic-associated diarrhea in outpatients-A systematic review and meta-analysis. Antibiotics. 2017;6(4):21. doi: 10.3390/antibiotics6040021
Jafarnejad S, Shab-Bidar S, Speakman JR, et al. Probiotics reduce the risk of antibiotic-associated diarrhea in adults (18-64 Years) but not the elderly (>65 years): A meta-analysis. Nutr Clin Pract Off Publ Am Soc Parenter Enter Nutr. 2016;31(4):502-513. doi: 10.1177/0884533616639399
Kale-Pradhan PB, Jassal HK, Wilhelm SM. Role of Lactobacillus in the prevention of antibiotic-associated diarrhea: a meta-analysis. Pharmacotherapy. 2010;30(2):119-126. doi: 10.1592/phco.30.2.119
Ritchie ML, Romanuk TN. A meta-analysis of probiotic efficacy for gastrointestinal diseases. PloS One. 2012;7(4):e34938. doi: 10.1371/journal.pone.0034938
Szajewska H, Mrukowicz J. Meta-analysis: non-pathogenic yeast Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea. Aliment Pharmacol Ther. 2005;22(5):365-372. doi: 10.1111/j.1365-2036.2005.02624.x
Videlock EJ, Cremonini F. Meta-analysis: probiotics in antibiotic-associated diarrhoea. Aliment Pharmacol Ther. 2012;35(12):1355-1369. doi: 10.1111/j.1365-2036.2012.05104.x
Johnston BC, Supina AL, Vohra S. Probiotics for pediatric antibiotic-associated diarrhea: a meta-analysis of randomized placebo-controlled trials. CMAJ. 2006;175(4):377-383. doi: 10.1503/cmaj.051603
Szajewska H, Ruszczyński M, Radzikowski A. Probiotics in the prevention of antibiotic-associated diarrhea in children: a meta-analysis of randomized controlled trials. J Pediatr. 2006;149(9):367-372. doi: 10.1016/j.jpeds.2006.04.053
Zhang L, Zeng X, Guo D, et al. Early use of probiotics might prevent antibiotic-associated diarrhea in elderly (>65 years): a systematic review and meta-analysis. BMC Geriatr. 2022;22(1):562. doi: 10.1186/s12877-022-03257-3
Avadhani A, Miley H. Probiotics for prevention of antibiotic-associated diarrhea and Clostridium difficile-associated disease in hospitalized adults-a meta-analysis. J Am Acad Nurse Pract. 2011;23(6):269-274. doi: 10.1111/j.1745-7599.2011.00617.x
Cremonini F, Di Caro S, Nista EC, et al. Meta-analysis: the effect of probiotic administration on antibiotic-associated diarrhoea. Aliment Pharmacol Ther. 2002;16(8):1461-1467. doi: 10.1046/j.1365-2036.2002.01318.x
Szajewska H, Kołodziej M. Systematic review with meta-analysis: Lactobacillus rhamnosus GG in the prevention of antibiotic-associated diarrhoea in children and adults. Aliment Pharmacol Ther. 2015;42(10):1149-1157. doi: 10.1111/apt.13404
Xu H-B, Jiang R-H, Sheng H-B. Meta-analysis of the effects of Bifidobacterium preparations for the prevention and treatment of pediatric antibiotic-associated diarrhea in China. Complement Ther Med. 2017;33:105-113. doi: 10.1016/j.ctim.2017.07.001
Businesswire. Global probiotics dietary supplements market report 2023: Sector is expected to reach $51.84 billion by 2030, https://www.businesswire.com/news/home/20230710251414/en/Global-Probiotics-Dietary-Supplements-Market-Report-2023-Sector-is-Expectedto-Reach-51.84-Billion-by-2030---ResearchAndMarkets.com. Accessed June 30, 2024.
Office of Dietary Supplements. Probiotics: fact sheet for health professionals. https://ods.od.nih.gov/factsheets/Probiotics-HealthProfessional/. Accessed June 30,2024.
de Simone C. The unregulated probiotic market. Clin Gastroenterol Hepatol. 2019;17(5):809-817.
Su GL, Ko CW, Bercik P, et al. AGA clinical practice guidelines on the role of probiotics in the management of gastrointestinal disorders. Gastroenterology. 2020;159(2):697-705. doi: 10.1053/j.gastro.2020.05.059
Verna EC, Lucak S. Use of probiotics in gastrointestinal disorders: what to recommend? Ther Adv Gastroenterol. 2010;3(5):307-319. doi: 10.1177/1756283X10373814
Doron S, Snydman DR. Risk and safety of probiotics. Clin Infect Dis. 2015;60(2):129-134. doi: 10.1093/cid/civ085
Yelin I, Flett KB, Merakou C, et al. Genomic and epidemiological evidence of bacterial transmission from probiotic capsule to blood in ICU patients. Nat Med. 2019;25(11):1728-1732. doi: 10.1038/s41591-019-0626-9
Besselink MG, van Santvoort HC, Buskens E, et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;371(9613):651-659. doi: 10.1177/0884533608326323
World Gastroenterology Organisation. Probiotics and prebiotics. https://www.worldgastroenterology.org/guidelines/probiotics-and-prebiotics. Accessed June 30, 2024.
Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of infectious diarrhea. Clin Infect Dis. 2017;65(12):45-80.
Lee YY, Leow AHR, Chai PF, et al. Use of probiotics in clinical practice with special reference to diarrheal diseases: A position statement of the Malaysian Society of Gastroenterology and Hepatology. JGH Open. 2021;5(1):11-19. doi: 10.1002/jgh3.12469
Szajewska H, Berni Canani R, Domellöf M, et al. Probiotics for the management of pediatric gastrointestinal disorders: Position paper of the ESPGHAN special interest group on gut microbiota and modifications. J Pediatr Gastroenterol Nutr. 2023;76(2):232-247. doi: 10.1097/MPG.0000000000003633
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 European Journal of Clinical and Experimental Medicine

This work is licensed under a Creative Commons Attribution 4.0 International License.
Our open access policy is in accordance with the Budapest Open Access Initiative (BOAI) definition: this means that articles have free availability on the public Internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from having access to the Internet itself.
All articles are published with free open access under the CC-BY Creative Commons attribution license (the current version is CC-BY, version 4.0). If you submit your paper for publication by the Eur J Clin Exp Med, you agree to have the CC-BY license applied to your work. Under this Open Access license, you, as the author, agree that anyone may download and read the paper for free. In addition, the article may be reused and quoted provided that the original published version is cited. This facilitates freedom in re-use and also ensures that Eur J Clin Exp Med content can be mined without barriers for the research needs.




