Штамм-специфичная эффективность Saccharomyces boulardii CNCM I-745 в профилактике антибиотик-ассоциированной диареи: систематический обзор и метаанализ

Цель: проведение систематического обзора и метаанализа эффективности применения Saccharomyces boulardii CNCM I-745 в профилактике антибиотик-ассоциированной диареи (ААД) у взрослых и детей.

Материалы и методы. Протокол данного систематического обзора и метаанализа был предварительно зарегистрирован в международной базе PROSPERO (CRD420261296647). В соответствии с рекомендациями PRISMA 2020 проведен систематический поиск публикаций в базах данных MEDLINE/PubMed, Embase, Cochrane Library, Scopus и РИНЦ с момента появления первых публикаций по 6 февраля 2026 г. Включались исследования, оценивающие эффективность S. boulardii CNCM I-745 (лекарственный препарат «Энтерол^®») в первичной профилактике ААД и инфекции Clostridioides difficile у взрослых и детей.

Результаты. В метаанализ было включено 29 исследований, соответствующих критериям включения. Применение S. boulardii CNCM I-745 было ассоциировано со статистически значимым снижением частоты ААД по сравнению с контролем в общем пуле исследований (отношение шансов [ОШ] 0,38; 95%-ный доверительный интервал [95% ДИ] 0,32–0,45). Анализ в подгруппах подтвердил эффективность пробиотика как у взрослых (20 исследований, n = 3937; ОШ 0,45; 95% ДИ 0,33–0,61), так и у детей, где эффект был еще более выраженным (7 исследований, n = 1608; ОШ 0,31; 95% ДИ 0,23–0,41). В анализе исследований, в которых S. boulardii CNCM I-745 применялся в составе схем эрадикации Helicobacter pylori, также было выявлено статистически значимое снижение риска ААД (13 исследований, n = 2333; ОШ 0,36; 95% ДИ 0,25–0,52). Дополнительный анализ продемонстрировал значимое снижение риска инфекции Clostridioides difficile на фоне приема S. boulardii CNCM I-745 (8 исследований, n = 18 426; ОШ 0,67; 95% ДИ 0,49–0,92).

Выводы. Результаты настоящего метаанализа демонстрируют высокую эффективность S. boulardii CNCM I-745 в профилактике ААД у взрослых и детей, а также снижении риска инфекции Clostridioides difficile на фоне антибиотикотерапии с первого дня ее проведения.

1. Leekha S., Terrell C.L., Edson R.S. General principles of antimicrobial therapy. Mayo Clin Proc. 2011;86(2):156–67. DOI: 10.4065/mcp.2010.0639

2. Mohsen S., Dickinson J.A., Somayaji R. Update on the adverse effects of antimicrobial therapies in community practice. Can Fam Physician. 2020;66(9):651–9.

3. McFarland L.V. Antibiotic-associated diarrhea: Epidemiology, trends and treatment. Future Microbiol. 2008;3(5):563–78. DOI: 10.2217/17460913.3.5.563

4. Pérez-Cobas A., Moya A., Gosalbes M., Latorre A. Colonization resistance of the gut microbiota against Clostridium difficile. Antibiotics (Basel). 2015;4(3):337–57. DOI: 10.3390/antibiotics4030337

5. Zhang L., Zeng X., Guo D., Zou Y., Gan H., Huang X. 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

6. Selvaraj V., Alsamman M.A. Antibiotic-associated diarrhea beyond C. difficile: A scoping review. Brown J Hosp Med. 2022;2(1):39745. DOI: 10.56305/001c.39745

7. Шаповалова М.М., Будневский А.В., Кравченко А.Я., Дробышева Е.С., Овсянников Е.С. Патогенез, современные аспекты профилактики и терапии антибиотик-ассоциированной диареи. Архивъ внутренней медицины. 2018;8(6):424–9. DOI: 10.20514/2226-6704-2018-8-6-424-429

8. Khanna S., Gupta A., Baddour L.M., Pardi D.S. Epidemiology, outcomes, and predictors of mortality in hospitalized adults with Clostridium difficile infection. Intern Emerg Med. 2016;11(5):657–65. DOI: 10.1007/s11739-015-1366-6

9. Motamedi H., Fathollahi M., Abiri R., Kadivarian S., Rostamian M., Alvandi A. A worldwide systematic review and meta-analysis of bacteria related to antibiotic-associated diarrhea in hospitalized patients. PLoS One. 2021;16(12):e0260667. DOI: 10.1371/journal.pone.0260667

10. Wanyama H., Akhtar T.S., Abbas S. Probiotic use reduces the incidence of antibiotic-associated diarrhea among adult patients: A meta-analysis. Prz Gastroenterol. 2025;20(1):5–16. DOI: 10.5114/pg.2025.148486

11. Esmaeilinezhad Z., Ghosh N.R., Walsh C.M., Steen J.P., Burgman A.M., Mertz D., et al. Probiotics for the prevention of Clostridioides difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2025;9(9):CD006095. DOI: 10.1002/14651858.CD006095.pub5

12. Kaźmierczak-Siedlecka K., Ruszkowski J., Fic M., Folwarski M., Makarewicz W. Saccharomyces boulardii CNCM I-745: A non-bacterial microorganism used as probiotic agent in supporting treatment of selected diseases. Curr Microbiol. 2020;77(9):1987–96. DOI: 10.1007/s00284-020-02053-9

13. Szajewska H., Kołodziej M. Systematic review with meta- analysis: Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea. Aliment Pharmacol Ther. 2015;42(7):793–801. DOI: 10.1111/apt.13344

14. McFarland L.V. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol. 2010;16(18):2202–22. DOI: 10.3748/wjg.v16.i18.2202

15. Duffey H.E., Hedin K.A., Gelli H.P., Vaaben T.H., Otto Alexander Sommer M. Genomic and phenotypic comparison of Saccharomyces cerevisiae and Saccharomyces boulardii. bioRxiv [Preprint]. 2025:2025.09.08.674931. DOI: 10.1101/2025.09.08.674931

16. Adam J., Barret A., Barret-Bellet C. Controlled double blind clinical trials of lyophilized Ultra-Levure. Multiplecenter study by 25 physicians of 388 cases. Gaz Med Fr. 1977;84:2072–8. (In French).

17. Monteiro E., Fernandes J.P., Vieira M.R., Correia J.P., Caetano J.M., Ribeiro T., et al. Double blind clinical trial on the use of ultra-levure in the prophylaxis of antibiotic induced gastro-intestinal and mucocutaneous disorders. Acta Med Port. 1981;3(2):143–5. [In Portuguese].

18. Surawicz C.M., Elmer G.W., Speelman P., McFarland L.V., Chinn J., Van Belle G. Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: A prospective study. Gastroenterology. 1989;96(4):981–8. DOI: 10.1016/0016-5085(89)91613-2

19. McFarland L.V., Surawicz C.M., Greenberg R.N., Elmer G.W., Moyer K.A., Melcher S.A., et al. Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo. Am J Gastroenterol. 1995;90(3):439–48.

20. Lewis S.J., Potts L.F., Barry R.E. The lack of therapeutic effect of Saccharomyces boulardii in the prevention of antibiotic-related diarrhoea in elderly patients. J Infect. 1998;36(2):171–4. DOI: 10.1016/S0163-4453(98)80008-X

21. Duman D.G., Bor S., Ozütemiz O., Sahin T., Oğuz D., Iştan F., et al. Efficacy and safety of Saccharomyces boulardii in prevention of antibiotic-associated diarrhoea due to Helicobacter pylori eradication. Eur J Gastroenterol Hepatol. 2005;17(12):1357–61. DOI: 10.1097/00042737-200512000-00015

22. Can M., Beşirbellioglu B.A., Avci I.Y., Beker C.M., Pahsa A. Prophylactic Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea: A prospective study. Med Sci Monit. 2006;12(4):PI19–22.

23. Cindoruk M., Erkan G., Karakan T., Dursun A., Unal S. Efficacy and safety of Saccharomyces boulardii in the 14day triple anti-Helicobacter pylori therapy: A prospective randomized placebo-controlled double-blind study. Helicobacter. 2007;12(4):309–16. DOI: 10.1111/j.1523-5378.2007.00516.x

24. Bravo M.V., Bunout D., Leiva L., de la Maza M.P., Barrera G., de la Maza J., et al. Effect of probiotic Saccharomyces boulardii on prevention of antibiotic-associated diarrhea in adult outpatients with amoxicillin treatment. Rev Med Chil. 2008;136(8):981–8. (In Spanish).

25. Chu Yi, Zhu H., Zhou Y., Lv L., Hu J. Intervention study on Saccharomyces boulardii with proton pump inhibitor (PPI)-based triple therapy for Helicobacter pylori related peptic ulcer. Afr J Pharm Pharmacol. 2012;6(41):2900–4. DOI: 10.5897/AJPP12.400

26. Pozzoni P., Riva A., Bellatorre A.G., Amigoni M., Redaelli E., Ronchetti A., et al. Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: A single-center, randomized, double-blind, placebo-controlled trial. Am J Gastroenterol. 2012;107(6):922–31. DOI: 10.1038/ajg.2012.56

27. Ehrhardt S., Guo N., Hinz R., Schoppen S., May J., Reiser M., et al. Saccharomyces boulardii to prevent antibiotic-associated diarrhea: A randomized, doublemasked, placebo-controlled trial. Open Forum Infect Dis. 2016;3(1):ofw011. DOI: 10.1093/ofid/ofw011

28. Chotivitayatarakorn P., Mahachai V., Vilaichone R.-K. Effectiveness of 7-day and 14-day moxifloxacin-dexlansoprazole based triple therapy and probiotic supplement for Helicobacter pylori eradication in Thai patients with non-ulcer dyspepsia: A double-blind randomized placebo-controlled study. Asian Pac J Cancer Prev. 2017;18(10):2839–43. DOI: 10.22034/APJCP.2017.18.10.2839

29. Seddik H., Boutallaka H., Elkoti I., Nejjari F., Berraida R., Berrag S., et al. Saccharomyces boulardii CNCM I-745 plus sequential therapy for Helicobacter pylori infections: A randomized, open-label trial. Eur J Clin Pharmacol. 2019;75(5):639–45. DOI: 10.1007/s00228-019-02625-0

30. Zhao Y., Yang Y., Aruna, Xiao J., Song J., Huang T., et al. Saccharomyces boulardii combined with quadruple therapy for Helicobacter pylori eradication decreased the duration and severity of diarrhea: A multi-center prospective randomized controlled trial. Front Med (Lausanne). 2021;8:776955. DOI: 10.3389/fmed.2021.776955

31. Маев И.В., Андреев Д.Н., Соколов Ф.С., Фоменко А.К., Девкота М.К., Андреев Н.Г. и др. Эффективность пробиотика Saccharomyces boulardii CNCM I-745 в рамках профилактики и лечения диареи у госпитализированных пациентов с новой коронавирусной инфекцией COVID-19. Терапевтический архив. 2022;94(10): 1163–70. DOI: 10.26442/00403660.2022.10.201881

32. He X.J., Wang X.L., Sun D.J., Huang X.Y., Liu G., Li D.Z., et al. The efficacy and safety of Saccharomyces boulardii in addition to antofloxacin-based bismuth quadruple therapy for Helicobacter pylori eradication: A single-center, prospective randomized-control study. Therap Adv Gastroenterol. 2023;16:17562848221147764. DOI: 10.1177/17562848221147763

33. Sjomina O., Poļaka I., Suhorukova J., Vangravs R., Paršutins S., Knaze V., et al. Randomised clinical trial: Efficacy and safety of H. pylori eradication treatment with and without Saccharomyces boulardii supplementation. Eur J Cancer Prev. 2024;33(3):217–22. DOI: 10.1097/CEJ.0000000000000858

34. Yu J., Cui C., Ma K., Yang P., Jiang Y., Wang X. Effectiveness and safety of vonoprazan and amoxicillin dual regimen with Saccharomyces boulardii supplements on eradication of Helicobacter pylori. BMC Gastroenterol. 2024;24(1):430. DOI: 10.1186/s12876-024-03524-0

35. Zhang Y., Lu B., Dong Y., Zhang Y., Du Q., Chen Y., et al. Saccharomyces boulardii combined with triple therapy alter the microbiota in the eradication of Helicobacter pylori infection. Sci Rep. 2024;14(1):13152. DOI: 10.1038/s41598-024-63894-z

36. Kotowska M., Albrecht P., Szajewska H. Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: A randomized double-blind placebo-controlled trial. Aliment Pharmacol Ther. 2005;21(5):583–90. DOI: 10.1111/j.1365-2036.2005.02356.x

37. Kyriakos N., Papamichae K., Roussos A., Theodoropoulo I., Karakoidas C., Smyrnidis A., et al. A lyophilized form of Saccharomyces boulardii enhances the Helicobacter pylori eradication rates of omeprazole-triple therapy in patients with peptic ulcer disease or functional dyspepsia. Hospital Chronicles. 2013;8(3):127–33. DOI: 10.2015/hc.v8i3.538

38. Shan L.S., Hou P., Wang Z.J., Liu F.R., Chen N., Shu L.H., et al. Prevention and treatment of diarrhoea with Saccharomyces boulardii in children with acute lower respiratory tract infections. Benef Microbes. 2013;4(4):329–34. DOI: 10.3920/BM2013.0008

39. Zhao H.M., Ou-Yang H.J., Duan B.P., Xu B., Chen Z.Y., Tang J., et al. Clinical effect of triple therapy combined with Saccharomyces boulardii in the treatment of Helicobacter pylori infection in children. Zhongguo Dang Dai Er Ke Za Zhi. 2014;16(3):230–3. (In Chinese).

40. Bin Z., Ya-Zheng X., Zhao-Hui D., Bo C., Li-Rong J., Vandenplas Y. The efficacy of Saccharomyces boulardii CNCM I-745 in addition to standard Helicobacter pylori eradication treatment in children. Pediatr Gastroenterol Hepatol Nutr. 2015;18(1):17. DOI: 10.5223/pghn.2015.18.1.17

41. Wan C.M., Yu H., Liu G., Xu H.M., Mao Z.Q., Xu Y., et al. A multicenter randomized controlled study of Saccharomyces boulardii in the prevention of antibioticassociated diarrhea in infants and young children. Zhonghua Er Ke Za Zhi 2017;55(5):349–54. (In Chinese). DOI: 10.3760/cma.j.issn.0578-1310.2017.05.008

42. Zhang S.W., Zhi X., Wang M.Y., Shen D.L. A prospective randomized controlled study on probiotics for the prevention of antibiotic-associated diarrhea in infants and young children. Zhongguo Dang Dai Er Ke Za Zhi. 2024;26(10):1108–14. (In Chinese). DOI: 10.7499/j.issn.1008-8830.2401129

43. Wombwell E., Patterson M.E., Bransteitter B., Gillen L.R. The effect of Saccharomyces boulardii primary prevention on risk of hospital-onset Clostridioides difficile infection in hospitalized patients administered antibiotics frequently associated with C. difficile infection. Clin Infect Dis. 2021;73(9):e2512–8. DOI: 10.1093/cid/ciaa808

44. Wombwell E. Saccharomyces boulardii prophylaxis for targeted antibiotics and infectious indications to reduce healthcare facility-onset Clostridioides difficile infection. Microbes Infect. 2023;25(3):105041. DOI: 10.1016/j.micinf.2022.105041

45. Kwon J., Kong Y., Wade M., Williams D.J., Creech C.B., Evans S., et al. Gastrointestinal microbiome disruption and antibiotic-associated diarrhea in children receiving antibiotic therapy for community-acquired pneumonia. J Infect Dis. 2022;226(6):1109–19. DOI: 10.1093/infdis/jiac082

46. Mullish B.H., Williams H.R. Clostridium difficile infection and antibiotic-associated diarrhoea. Clin Med (Lond). 2018;18(3):237–41. DOI: 10.7861/clinmedicine.18-3-237

47. Turner N.A., Krishnan J., Nelson A., Polage C.R., Sinkowitz-Cochran R.L., Fike L., et al. CDC’s hospital-onset Clostridioides difficile prevention framework in a regional hospital network. JAMA Netw Open. 2024;7(3):e243846. DOI: 10.1001/jamanetworkopen.2024.3846

48. Kopacz K., Phadtare S. Probiotics for the prevention of antibiotic-associated diarrhea. Healthcare (Basel). 2022;10(8):1450. DOI: 10.3390/healthcare10081450

49. Maslennikov R., Gosteeva E., Ananeva V., Korshunova L., Kravtsowa A., Poluektova E., et al. Strain-specific systematic review with meta-analysis of probiotics efficacy in the treatment of irritable bowel syndrome. J Clin Med. 2026;15(3):1152. DOI: 10.3390/jcm15031152

50. McFarland L.V., Li T. Saccharomyces boulardii CNCM I-745 for prevention of antibiotic-associated diarrhea and Clostridioides difficile in China: Systematic review and meta-analysis. J Dig Dis Hepatol. 2024;9(1):208. DOI: 10.29011/2574-3511.100208

51. FAO/WHO. Guidelines for the evaluation of probiotics in food: Report of a joint FAO/WHO Working Group on drafting guidelines for the evaluation of probiotics in food. Ontario: 2002. URL: https://isappscience.org/wp-content/uploads/2019/04/probiotic_guidelines.pdf

52. Guarner F., Sanders M.E., Szajewska H., Cohen H., Eliakim R., Herrera-deGuise C., et al. World Gastroenterology Organisation global guidelines: Probiotics and prebiotics. J Clin Gastroenterol. 2024;58(6):533–53. DOI: 10.1097/MCG.0000000000002002

53. Szajewska H., Berni Canani R., Domellöf M., Guarino A., Hojsak I., Indrio F., et al. Probiotics for the management of pediatric gastrointestinal disorders. J Pediatr Gastroenterol Nutr. 2023;76(2):232–47. DOI: 10.1097/MPG.0000000000003633

54. Rachina S., Belkova Y., Kozlov R., Kurkova A., Boven A., Versporten A., et al. Antimicrobial prescribing patterns in Russian outpatients in 2024: Results of the GlobalPPS project. Infect Chemother. 2025;57(2):261–73. DOI: 10.3947/ic.2024.0144

55. Hicks L.A., Bartoces M.G., Roberts R.M., Suda K.J., Hunkler R.J., Taylor T.H., et al. US outpatient antibiotic prescribing variation according to geography, patient population, and provider specialty in 2011. Clin Infect Dis. 2015;60(9):1308–16. DOI: 10.1093/cid/civ076

56. Sohn M., Pontefract B., Dahal K., Klepser M. Outpatient antibiotic stewardship during the COVID-19 era: Analysis of prescribing trends and guideline compliance. Antimicrob Steward Healthc Epidemiol. 2025;5(1):e168. DOI: 10.1017/ash.2025.10081

57. Andreev D.N., Khurmatullina A.R., Maev I.V., Bordin D.S., Abdulkhakov S.R., Kucheryavyy Y.A., et al. The prevalence of Helicobacter pylori infection in the adult population of Russia: A systematic review and meta-ana- lysis. Epidemiologia (Basel). 2025;6(3):47. DOI: 10.3390/epidemiologia6030047

58. Андреев Д.Н., Хурматуллина А.Р., Бордин Д.С., Маев И.В. Динамика распространенности инфекции Helicobacter pylori у взрослого населения Москвы: систематический обзор и метаанализ. Терапевтический архив. 2025;97(5):463–70. DOI: 10.26442/00403660.2025.05.203250

59. Andreev D.N., Khurmatullina A.R., Maev I.V., Bordin D.S., Zaborovskiy A.V., Abdulkhakov S.R., et al. Helicobacter pylori antibiotic resistance in Russia: A systematic review and meta-analysis. Antibiotics (Basel). 2025;14(5):524. DOI: 10.3390/antibiotics14050524

60. Malfertheiner P., Megraud F., Rokkas T., Gisbert J.P., Liou J.-M., Schulz C., et al.; European Helicobacter and Microbiota Study group. Management of Helicobacter pylori infection: The Maastricht VI/Florence consensus report. Gut. 2022:gutjnl-2022-327745. DOI: 10.1136/gutjnl-2022-327745

61. Андреев Д.Н., Хурматуллина А.Р., Бордин Д.С., Заборовский А.В., Лямина С.В., Абдулхаков С.Р. и др. Характеристика кларитромицин-резистентных штаммов Helicobacter pylori в России: систематический обзор и метаанализ. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2025;35(4):60–70.DOI: 10.22416/1382-4376-2025-35-4-60-70

62. Маев И.В., Кучерявый Ю.А., Андреев Д.Н., Баркалова Е.В. Эрадикационная терапия инфекции Helicobacter pylori: обзор мировых тенденций. Терапевтический архив. 2014;86(3):94–9.

63. Maev I.V., Andreev D.N., Kucheryavyi Yu.A., Dicheva D.T. Host factors influencing the eradication rate of Helicobacter pylori. World Applied Sci J. 2014;30(30): 134–40. DOI: 10.5829/idosi.wasj.2014.30.mett.61

64. Huguet J.M., Ferrer-Barceló L., Suárez P., Barcelo-Cerda S., Sempere J., Saracino I.M., et al. Role of compliance in Helicobacter pylori eradication treatment: Results of the European Registry on H. pylori management. United European Gastroenterol J. 2024;12(6):691–704. DOI: 10.1002/ueg2.12569

65. Nyssen O.P., Jonaitis L., Pérez-Aísa Á., Tepes B., Mahmudov U., Voynovan I., et al.; Hp-EuReg investigators. Real-world effectiveness and safety of Saccharomyces boulardii CNCM I-745 as adjunct therapy for Helicobacter pylori eradication: Data from the European Registry on H. pylori management (Hp-EuReg). Helicobacter. 2026;31(2):e70119. DOI: 10.1111/hel.70119

66. Czerucka D., Rampal P. Diversity of Saccharomyces boulardii CNCM I-745 mechanisms of action against intestinal infections. World J Gastroenterol. 2019;25(18):2188–203. DOI: 10.3748/wjg.v25.i18.2188

67. Im E., Pothoulakis C. Recent advances in Saccharomyces boulardii research. Gastroenterol Clin Biol. 2010;34(Suppl 1):S62–70. (In French). DOI: 10.1016/S0399-8320(10)70023-3

68. Castagliuolo I., LaMont J.T., Nikulasson S.T., Pothoulakis C. Saccharomyces boulardii protease inhibits Clostridium difficile toxin A effects in the rat ileum. Infect Immun. 1996;64(12):5225–32. DOI: 10.1128/iai.64.12.5225-5232.1996

69. Castagliuolo I., Riegler M.F., Valenick L., LaMont J.T., Pothoulakis C. Saccharomyces boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human colonic mucosa. Infect Immun. 1999;67(1):302–7. DOI: 10.1128/IAI.67.1.302-307.1999

70. Qamar A., Aboudola S., Warny M., Michetti P., Pothoulakis C., LaMont J.T., et al. Saccharomyces boulardii stimulates intestinal immunoglobulin A immune response to Clostridium difficile toxin A in mice. Infect Immun. 2001;69(4):2762–5. DOI: 10.1128/IAI.69.4.2762-2765.2001

71. Huang Z., Brot L., Fatouh R., Bredon M., Creusot L., Lefèvre A., et al. Saccharomyces boulardii CNCM I-745 mitigates antibiotic-induced gut microbiome functional alterations independently of the host. Gut Microbes. 2025;17(1):2575924. DOI: 10.1080/19490976.2025.2575924

72. Filipe Rosa L., Gonda S., Roese N., Bischoff S.C. Saccharomyces boulardii CNCM I-745 supernatant improves markers of gut barrier function and inflammatory response in small intestinal organoids. Pharmaceuticals (Basel). 2025;18(8):1167. DOI: 10.3390/ph18081167