Advantages of multi-strain probiotics in the treatment of infectious diseases in children

The article is devoted to the study of probiotics, their principle of action and clinical application. Particular attention is paid to the mechanisms of action of probiotics, including competition with pathogens in nutrient substrates and adhesion sites, synthesis of antimicrobial metabolites (bacteriocins, organic acids), intestinal barrier and modulation of the immune response. Additional considerations of the risks of using probiotics, including the possibility of developing systemic diseases, metabolic abilities and hyperstimulation of the immune system. The need for strict control of the safety of strains, including their identification, study of functional activity and confirmation of effectiveness in randomized economic studies is emphasized. Particular attention is paid to the benefits of multi-strain probiotics, which exhibit a synergistic effect due to different strains that increase therapeutic efficacy. In providing research data confirming their benefits in the fight against intestinal infections, antibiotic-associated diarrhea, respiratory diseases and other conditions. 14 species of live probiotic bacteria in high concentrations: L. casei, L. plantarum, L. rhamnosus, B. bifidum, B. breve, B. longum, L. acidophilus, L. lactis, St. thermophilus, B. infantis, L. bulgaricus, L. helveticus, L. salivarius, L. fermentum in the studies confirmed the ability to significantly increase the effectiveness of standard treatment for diarrhea regardless of etiology, reducing the risk of prolonged diarrhea. Eight studies demonstrated that multi-strain probiotics enhanced immune defense and protective properties of the mucous membranes in both infectious diarrhea and respiratory diseases. The results of the conducted analysis indicate the importance of using multi-strain probiotics for the prevention and treatment of infectious diseases in children, but it is necessary to monitor the need for research to clarify their long-term effects and safety.

1. Fuller R. Probiotics in man and animals. J Appl Bacteriol. 1989;66(5):365‒378. Available at: https://www.sci-hub.ru/10.1111/j.1365-2672.1989.tb05105.x.

2. Mazankova LN, Lykova EA. Probiotics: characteristics of drugs and choice in pediatric practice. Children Infections. 2004;(1):18‒23. (In Russ.) Available at: https://elibrary.ru/kapqzd.

3. Saarela M, Mogensen G, Fondén R, Mättö J, Mattila-Sandholm T. Probiotic bacteria: safety, functional and technological properties. J Biotechnol. 2000;84(3):197‒215. https://doi.org/10.1016/s0168-1656(00)00375-8.

4. Saarela MH. Safety aspects of next generation probiotics. Curr Opin Food Sci. 2019;30:8‒13. https://doi.org/10.1016/j.cofs.2018.09.001.

5. Goldenberg JZ, Yap C, Lytvyn L, Lo CK, Beardsley J, Mertz D, Johnston BC. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12(12):CD006095. https://doi.org/10.1002/14651858.CD006095.pub4.

6. Reid G, Jass J, Sebulsky MT, McCormick JK. Potential uses of probiotics in clinical practice. Clin Microbiol Rev. 2003;16(4):658‒672. https://doi.org/10.1128/CMR.16.4.658-672.2003.

7. Shewale RN, Sawale PD, Khedkar C, Singh A. Selection criteria for probiotics: A review. Int J Probiotics Prebiotics. 2014;9(1):17‒22. Available at: https://www.researchgate.net/publication/288067379_Selection_criteria_ for_probiotics_A_review.

8. Klaenhammer TR, Kullen MJ. Selection and design of probiotics. Int J Food Microbiol. 1999;50(1-2):45‒57. https://doi.org/10.1016/s01681605(99)00076-8.

9. Aucott JN, Fayen J, Grossnicklas H, Morrissey A, Lederman MM, Salata RA. Invasive infection with Saccharomyces cerevisiae: report of three cases and review. Rev Infect Dis. 1990;12(3):406‒411. https://doi.org/10.1093/clinids/12.3.406.

10. Santino I, Alari A, Bono S, Teti E, Marangi M, Bernardini A et al. Saccharomyces cerevisiae fungemia, a possible consequence of the treatment of Clostridium difficile colitis with a probioticum. Int J Immunopathol Pharmacol. 2014;27(1):143‒146. https://doi.org/10.1177/039463201402700120.

11. Ishida N, Suzuki T, Tokuhiro K, Nagamori E, Onishi T, Saitoh S et al. D-lactic acid production by metabolically engineered Saccharomyces cerevisiae. J Biosci Bioeng. 2006;101(2):172‒177. https://doi.org/10.1263/jbb.101.172.

12. Baek SH, Kwon EY, Bae SJ, Cho BR, Kim SY, Hahn JS. Improvement of D-Lactic Acid Production in Saccharomyces cerevisiae Under Acidic Conditions by Evolutionary and Rational Metabolic Engineering. Biotechnol J. 2017;12(10):1700015. https://doi.org/10.1002/biot.201700015.

13. Van den Nieuwboer M, Brummer RJ, Guarner F, Morelli L, Cabana M, Claasen E. The administration of probiotics and synbiotics in immune compromised adults: is it safe? Benef Microbes. 2015;6(1):3‒17. https://doi.org/10.3920/BM2014.0079.

14. Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi SJ et al. Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods. 2019;8(3):92. https://doi.org/10.3390/foods8030092.

15. Latif A, Shehzad A, Niazi S, Zahid A, Ashraf W, Iqbal MW et al. Probiotics: mechanism of action, health benefits and their application in food industries. Front Microbiol. 2023;14:1216674. https://doi.org/10.3389/fmicb.2023.1216674.

16. Mazziotta C, Tognon M, Martini F, Torreggiani E, Rotondo JC. Probiotics Mechanism of Action on Immune Cells and Beneficial Effects on Human Health. Cells. 2023;12(1):184. https://doi.org/10.3390/cells12010184.

17. Plaza-Diaz J, Ruiz-Ojeda FJ, Gil-Campos M, Gil A. Mechanisms of Action of Probiotics. Adv Nutr. 2019;10(Suppl. 1):S49‒S66. https://doi.org/10.1093/advances/nmy063.

18. Markowiak-Kopeć P, Śliżewska K. The Effect of Probiotics on the Production of Short-Chain Fatty Acids by Human Intestinal Microbiome. Nutrients. 2020;12(4):1107. https://doi.org/10.3390/nu12041107.

19. Martínez-Guardado I, Arboleya S, Grijota FJ, Kaliszewska A, Gueimonde M, Arias N. The Therapeutic Role of Exercise and Probiotics in Stressful Brain Conditions. Int J Mol Sci. 2022;23(7):3610. https://doi.org/10.3390/ijms23073610.

20. Purton T, Staskova L, Lane MM, Dawson SL, West M, Firth J et al. Prebiotic and probiotic supplementation and the tryptophan-kynurenine pathway: A systematic review and meta analysis. Neurosci Biobehav Rev. 2021;123:1‒13. https://doi.org/10.1016/j.neubiorev.2020.12.026.

21. Gu Q, Li P. Biosynthesis of Vitamins by Probiotic Bacteria. In: Rao A, Rao L (eds.). Probiotics and Prebiotics in Human Nutrition and Health. InTech; 2016, pp. 135‒148. https://doi.org/10.5772/63117.

22. Madsen K. Probiotics and the immune response. J Clin Gastroenterol. 2006;40(3):232‒234. https://doi.org/10.1097/00004836-200603000-00014.

23. Rautava S, Arvilommi H, Isolauri E. Specific probiotics in enhancing maturation of IgA responses in formula-fed infants. Pediatr Res. 2006;60(2):221‒224. https://doi.org/10.1203/01.pdr.0000228317.72933.db.

24. Capurso L. Thirty Years of Lactobacillus rhamnosus GG: A Review. J Clin Gastroenterol. 2019;53(Suppl. 1):S1‒S41. https://doi.org/10.1097/MCG.0000000000001170.

25. Maldonado Galdeano C, Cazorla SI, Lemme Dumit JM, Vélez E, Perdigón G. Beneficial Effects of Probiotic Consumption on the Immune System. Ann Nutr Metab. 2019;74(2):115‒124. https://doi.org/10.1159/000496426.

26. Ashraf R, Shah NP. Immune system stimulation by probiotic microorganisms. Crit Rev Food Sci Nutr. 2014;54(7):938‒956. https://doi.org/10.1080/10408398.2011.619671.

27. Mahajan M, Manjot K. Probiotics and health benefits: A review. Int J Food Nutr Sci. 2022;11(6):117‒125. Available at: https://ijfans.org/issue-content/probiotics-and-health-benefits-a-review-631.

28. Sanders ME, Merenstein DJ, Reid G, Gibson GR, Rastall RA. Probiotics and prebiotics in intestinal health and disease: from biology to the clinic. Nat Rev Gastroenterol Hepatol. 2019;16(10):605‒616. https://doi.org/10.1038/s41575-019-0173-3.

29. Allen SJ, Martinez EG, Gregorio GV, Dans LF. Probiotics for treating acute infectious diarrhoea. Cochrane Database Syst Rev. 2010;2010(11):CD003048. https://doi.org/10.1002/14651858.CD003048.pub3.

30. Arora T, Singh S, Sharma RK. Probiotics: Interaction with gut microbiome and antiobesity potential. Nutrition. 2013;29(4):591‒596. https://doi.org/10.1016/j.nut.2012.07.017.

31. Brüssow H. Probiotics and prebiotics in clinical tests: an update. F1000Res. 2019;8:F1000 Faculty Rev-1157. https://doi.org/10.12688/f1000research.19043.1.

32. Szajewska H, Berni Canani R, Domellöf M, Guarino A, Hojsak I, Indrio F 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. https://doi.org/10.1097/MPG.0000000000003633.

33. Claus SP, Guillou H, Ellero-Simatos S. The gut microbiota: a major player in the toxicity of environmental pollutants? NPJ Biofilms Microbiomes. 2016;2:16003. https://doi.org/10.1038/npjbiofilms.2016.3.

34. Corr SC, Hill C, Gahan CG. Understanding the mechanisms by which probiotics inhibit gastrointestinal pathogens. Adv Food Nutr Res. 2009;56:1‒15. https://doi.org/10.1016/S1043-4526(08)00601-3.

35. Solov’eva OI, Simanenkov VI, Suvorov AN, Ermolenko EI, Shumihina IA, Svirido DA. The use of probiotics and autoprobiotics in the treatment of irritable bowel syndrome. Experimental and Clinical Gastroenterology. 2017;(7):115‒120. (In Russ.) Available at: https://www.nogr.org/jour/article/view/460/459.

36. Das NC, Patra R, Dey A, Mukherjee S. Probiotics as Efficacious Therapeutic Option for Treating Gut-Related Diseases: Molecular and Immunobiological Perspectives. In: Behera KK, Bist R, Mohanty S, Bhattacharya M (eds.). Prebiotics, Probiotics and Nutraceuticals. Singapore: Springer; 2022, pp. 69–93. https://doi.org/10.1007/978-981-16-8990-1_5.

37. Bermudez-Brito M, Plaza-Díaz J, Muñoz-Quezada S, Gómez-Llorente C, Gil A. Probiotic mechanisms of action. Ann Nutr Metab. 2012;61(2):160–174. https://doi.org/10.1159/000342079.

38. Grandy G, Medina M, Soria R, Terán CG, Araya M. Probiotics in the treatment of acute rotavirus diarrhoea. A randomized, double-blind, controlled trial using two different probiotic preparations in Bolivian children. BMC Infect Dis. 2010;10:253. https://doi.org/10.1186/1471-2334-10-253.

39. Mileti E, Matteoli G, Iliev ID, Rescigno M. Comparison of the immunomodulatory properties of three probiotic strains of Lactobacilli using complex culture systems: prediction for in vivo efficacy. PLoS ONE. 2009;4(9):e7056. https://doi.org/10.1371/journal.pone.0007056.

40. Giacchi V, Sciacca P, Betta P. Multistrain probiotics: the present forward the future. In: Watson RR, Preedy VR (eds.). Probiotics, Prebiotics, and Synbiotics. Bioactive Foods in Health Promotion. Academic Press; 2016, pp. 279‒302. https://doi.org/10.1016/B978-0-12-802189-7.00019-8.

41. Vassilopoulou L, Spyromitrou-Xioufi P, Ladomenou F. Effectiveness of probiotics and synbiotics in reducing duration of acute infectious diarrhea in pediatric patients in developed countries: a systematic review and meta-analysis. Eur J Pediatr. 2021;180(9):2907‒2920. https://doi.org/10.1007/s00431-021-04046-7.

42. Tremblay A, Bronner S, Binda S. Review and Perspectives on Bifidobacterium lactis for Infants’ and Children’s Health. Microorganisms. 2023;11(10):2501. https://doi.org/10.3390/microorganisms11102501.

43. Subbotina MD, Chernova TM. Advantages of multi-strain bac-set probiotic complex in microcological disorders’ correction in acute diarrhea in children. Effective Pharmacotherapy. 2016;(16):6‒13. (In Russ.) Available at: https://www.elibrary.ru/whoptr.

44. Lang FC. Use of a multi-species probiotic: For the prevention of antibiotic associated diarrhea. Nutrafoods. 2010;9(2):27‒31. https://doi.org/10.1007/BF03223333.

45. Zoppi G, Cinquetti M, Benini A, Bonamini E, Minelli EB. Modulation of the intestinal ecosystem by probiotics and lactulose in children during treatment with ceftriaxone. Curr Ther Res. 2001;62(5):418‒435. https://doi.org/10.1016/S0011-393X(01)89006-8.

46. Gorelov AV, Melekhina EV, Sidel’nikova ES. Prevention of biocenosis imbalance in children with acute upper respiratory tract infection receiving antibacterial treatment. RMJ. 2019;(10):26‒31. (In Russ.) Available at: https://www.rmj.ru/articles/infektsionnye_bolezni/Profilaktika_narusheniy_biocenoza_u_detey_s_ostrymi_respiratornymi_infekciyami_poluchayuschih_antibakterialynuyu_terapiyu/.

47. Gorelov AV, Kanner EV, Melekhina ЕV, Sidelnikova ES. Improving preventive microbiome-sparing therapy in children with acute respiratory infections receiving antibiotics. Clinical Practice in Pediatrics. 2020;15(2):41‒50. (In Russ.) https://doi.org/10.20953/1817-7646-2020-2-41-50.