Lactobacillus rhamnosus GG: опыт применения в детской гастроэнтерологической практике

Организм человека с позиций современной науки принято рассматривать как симбиотический макроорганизм, число микробов-комменсалов которого во много раз превышает количество клеток самого хозяина. Нормальная микробиота человека принимает участие во многих физиологических процессах организма, а нарушение композиционного и качественного ее состава ассоциированы с развитием ряда заболеваний. Накопленные сведения о составе нормального микробиома позволили предположить, что его модификация может изменить течение заболевания, что положило начало изучению пробиотиков. Одним из наиболее изученных пробиотических штаммов является Lactobacillus rhamnosus GG (LGG), ATCC 53103, выделенный в 1985 г. Благодаря устойчивости штамма к кислоте и желчи, хорошим характеристикам роста и способности адгезироваться на кишечном эпителиальном слое, L. rhamnosus GG наиболее широко применяется в различных коммерчески доступных пробиотических продуктах. В статье приводятся обзор литературы, посвященной исследованиям данного пробиотика в различных схемах терапии и профилактики патологии желудочно-кишечного тракта у детей, в частности современные доказательства эффективности L. rhamnosus GG в терапии острого гастроэнтерита, антибиотик-ассоциированной диареи, а также результаты исследований при некротизирующем энтероколите, функциональных нарушениях кишечника, в схемах эрадикационной терапии при инфекции, вызванной Helicobacter pylori.

1. Jandhyala S.M. Role of the normal gut microbiota. World J Gastroenterol 2015; 21(29): 8787. DOI: 10.3748/wjg.v21.i29.8787

2. Pickard J.M., Zeng M.Y., Caruso R., Núñez G. Gut microbiota: Role in pathogen colonization, immune responses, and inflammatory disease. Immunol Rev 2017; 279(1): 70–89. DOI: 10.1111/imr.12567

3. World Gastroenterology Organization practice guideline: Probiotics and prebiotics. Arab J of Gastroenterol 2009; 10(1): 33–42.

4. Doron S., Snydman D.R., Gorbach S.L. Lactobacillus GG: Bacteriology and Clinical Applications. Gastroenterol Clin North Am 2005; 34(3): 483–498. DOI: 10.1016/j.gtc.2005.05.011

5. https://patents.google.com/patent/US4839281A/de

6. http://www.lactogg.com.cn/company.asp?fid=22&index=5

7. Goldin B.R., Gorbach S.L., Saxelin M., Barakat S., Gualtieri L., Salminen S. Survival of Lactobacillus species (strain GG) in human gastrointestinal tract. Dig Dis Sci 1992; 37 (1): 121–128. DOI: 10.1007/bf01308354

8. Capurso L. Thirty Years of Lactobacillus rhamnosus GG. J Clin Gastroenterol 2019; 53: 1–41. DOI: 10.1097/mcg.0000000000001170

9. Segers M.E., Lebeer S. Towards a better understanding of Lactobacillus rhamnosus GG – host interactions. Microb Cell Fact 2014; 13(Suppl 1): 7. DOI: 10.1186/1475-2859-13-s1-s7

10. Vélez M.P., Petrova M.I., Lebeer S., Verhoeven T.L.A., Claes I., Lambrichts I., De Keersmaecker S.C.J. Characterization of MabA, a modulator of Lactobacillus rhamnosus GG adhesion and biofilm formation. FEMS Immunol Med Microbiol 2010; 59(3): 386–398. DOI: 10.1111/j.1574-695x.2010.00680.x

11. Lu R., Fasano S., Madayiputhiya N., Morin N.P., Nataro J., Fasano A. Isolation, Identification, and Characterization of Small Bioactive Peptides From Lactobacillus GG Conditional Media That Exert Both Anti-Gram-negative and Gram-positive Bactericidal Activity. J Pediatr Gastroenterol Nutr 2009; 49(1): 23–30. DOI: 10.1097/mpg.0b013e-3181924d1e

12. Wang Y., Liu L., Moore D.J., Shen X., Peek R.M., Acra S.A., et al. A LGG-derived protein promotes IgA production through up-regulation of APRIL expression in intestinal epithelial cells. Mucosal Immunol 2017; 10: 373–384. DOI: 10.1038/mi.2016.57

13. Li N., Russell W.M., Douglas-Escobar M., Hauser N., Lopez M., Neu J. Live and heat-killed Lactobacillus rhamnosus GG: effects on proinflammatory and anti-inflammatory cytokines/ chemokines in gastrostomy-fed infant rats. Pediatr Res 2009; 66(2): 203–207. DOI: 10.1203/PDR.0b013e3181aabd4f

14. Savijoki K., Lietze’n N., Kankainen M., Alatossava T., Koskenniemi K., Varmanen P., Nyman T.A. Comparative Proteome Cataloging of Lactobacillus rhamnosus Strains GG and Lc705. J Proteome Res 2011; 10 (8): 3460–3473. DOI: 10.1021/pr2000896

15. Donato K.A., Gareau M.G., Wang Y.J.J., Sherman P.M. Lactobacillus rhamnosus GG attenuates interferonand tumour necrosis factor-induced barrier dysfunction and pro-inflammatory signalling. Microbiol 20

16. https://www.who.int/immunization/diseases/rotavirus/ru/ Актуальна на 20.12.19.

17. Guarino A., Ashkenazi S., Gendrel D., Lo Vecchio A., Shamir R., Szajewska H. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition / European Society for Pediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe: update 2014. J Pediatr Gastroenterol Nutr 2014; 59: 132–152.

18. Guandalini S., Pensabene L., Zikri M.A., Dias J.A., Casali L.G., Hoekstra H. et al. Lactobacillus GG administered in oral rehydration solution to children with acute diarrhea: a multicenter European trial. J Pediatr Gastroenterol Nutr 2000; 30: 54–60.

19. Huang J., Bousvaros A., Lee J., Diaz A., Davidson E.J. Efficacy of probiotic use in acute diarrhea in children, a meta-analysis. Dig Dis Sci 2002; 47(11): 2625–2634.

20. Guarino A., Guandalini S., Lo Vecchio A. Probiotics for prevention and treatment of diarrhea. J Clin Gastroenterol 2015; 49(Suppl. 1): 37–45. DOI: 10.1097/MCG.0000000000000349

21. Vandenplas Y. Probiotics and prebiotics in infectious gastroenteritis. Best Pract Res Clin Gastroenterol 2016; 30(1): 49–53. DOI: 10.1016/j.bpg.2015.12.002

22. Schnadower D., Tarr P.I., Casper T.C., Gorelick M.H., Dean J.M., O’Connell K.J. et al. Lactobacillus rhamnosus GG versus placebo for acute gastroenteritis in children. N Engl J Med 2018; 379: 2002–2014. DOI: 10.1056/NEJMoa1802598

23. Szajewska H., Kołodziej M., Gieruszczak-Białek D., Skórka A., Ruszczyński M., Shamir R. Systematic review with meta-analysis: Lactobacillus rhamnosus GG for treating acute gastroenteritis in children – a 2019 update. Aliment Pharmacol Ther 2019; 49: 1376–1384. DOI: 10.1111/apt.15267

24. Allen S.J., Martinez E.G., Gregorio G.V., Dans L.F. Probiotics for treating acute infectious diarrhoea. Cochrane Database Syst Rev 2010, Issue 11. Art. No.: CD003048. DOI: 10.1002/14651858.CD003048.pub3

25. World Health Organization. WHO definition of diarrhea. Accessed on November 13. 2015. Available from: http://www.who.int/topics/diarrhoea/en

26. McFarland L.V., Ozen M., Dinleyici E.C., Goh S. Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections. World J Gastroenterol 2016; 22(11): 3078. DOI: 10.3748/wjg.v22.i11.3078

27. Захарова И.Н., Бережная И.В., Сугян Н.Г. Антибиотик-ассоциированные диареи у детей: что нового? Медицинский совет 2017; 19: 126–133.

28. Hurley B.W., Nguyen C.C. The spectrum of pseudomembranous enterocolitis and antibiotic-associated diarrhea. Arch Intern Med 2002; 28: 2177–2184.

29. Czepiel J., Dróżdż M., Pituch H., Kuijper E.J., Perucki W., Mielimonka A. et al. Clostridium difficile infection: review. Eur J Clin Microbiol Infect Dis 2019; 38(7): 1211–1221. DOI: 10.1007/s10096-019-03539-6

30. Vanderhoof J.A., Whitney D.B., Antonson D.L., Hanner T.L., Lupo J.V., Young R.J. Lactobacillus GG in the prevention of antibiotic-associated diarrhea in children. J Pediatr 1999; 135(5): 564–568.

31. Perceval C., Szajewska H., Indrio F., Weizman Z., Vandenplas Y. Prophylactic use of probiotics for gastrointestinal disorders in children. Lancet Child Adolesc Health 2019; S2352–4642(19): 30182–30188. DOI: 10.1016/s2352-4642(19)30182-8

32. Hawrelak J.A., Whitten D.L., Myers S.P. Is Lactobacillus rhamnosus GG effective in preventing the onset of antibiotic-associated diarrhoea: a systematic review. Digestion 2005; 72: 51–56.

33. Johnston B.C., Supina A.L., Vohra S. Probiotics for pediatric antibiotic-associated diarrhea: a meta-analysis of randomized placebo-controlled trials. CMAJ 2006; 175(4): 377–383.

34. McFarland L.V. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol. 2006; 101: 812–822.

35. 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

36. Goldenberg J.Z., Lytvyn L., Steurich J., Parkin P., Mahant S., Johnston B.C. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev 2015; 12: CD004827. DOI: 10.1002/14651858.CD004827.pub4

37. Blaabjerg S., Artzi D.M., Aabenhus R. Probiotics for the prevention of antibiotic-associated diarrhea in outpatients–a systematic review and meta-analysis. Antibiotics 2017; 6(4). pii: E21. DOI: 10.3390/antibiotics6040021

38. Szajewska H., Canani R.B., Guarino A., Hojsak I., Indrio F., Kolacek S. et al. ESPGHAN Working Group for Probiotics Prebiotics. Probiotics for the Prevention of Antibiotic-Associated Diarrhea in Children. J Pediatr Gastroenterol Nutr 2016; 62(3): 495–506. DOI: 10.1097/MPG.0000000000001081

39. Guo Q., Goldenberg J.Z., Humphrey C., El Dib R., Johnston B.C. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev 2019; 4: CD004827. DOI: 10.1002/14651858.CD004827.pub5

40. Turck D., Bernet J.P., Marx J., Kempf H., Giard P., Walbaum O. et al. Incidence and risk factors of oral antibiotic-associated diarrhea in an outpatient pediatric population. J Pediatr Gastroenterol Nutr 2003; 37: 22–26.

41. Guarino A., Albano F., Ashkenazi S., Gendrel D., Hoekstra J.H., Shamir R., Szajewska H. European Society for Paediatric Gastroenterology, Hepatology, and Nutrition European Society for Paediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe. J Pediatr Gastroenterol Nutr 2008; 46(Suppl. 2): 81–122. DOI: 10.1097/MPG.0b013e31816f7b16

42. Szajewska H., Wanke M., Patro B. Meta-analysis: the effects of Lactobacillus rhamnosus GG supplementation for the prevention of healthcare-associated diarrhoea in children. Aliment Pharmacol Ther 2011; 34(9): 1079–1087. DOI: 10.1111/j.1365-2036.2011.04837.x

43. Basu S., Chatterjee M., Ganguly S., Chandra P.K. Effect of lactobacillus rhamnosus GG in persistent diarrhea in Indian children. J Clin Gastroenterol 2007; 41(8): 756–760. DOI: 10.1097/01.mcg.0000248009.47526.ea

44. Persistent diarrhoea in children in developing countries: memorandum from a WHO Meeting. Bull World Health Organization 1988; 66(6): 709–717.

45. Fundora J.B., Guha P., Shores D.R., Pammi M., Maheshwari A. Intestinal dysbiosis and necrotizing enterocolitis: assessment for causality using Bradford Hill criteria. Pediatr Res 2019. DOI: 10.1038/s41390-019-0482-9

46. Alfaleh K., Anabrees J. Probiotics for prevention of necrotizing enterocolitis in preterm infants (review). Cochrane Database Syst Rev 2014; Issue 4. Art. No.: CD005496. DOI: 10.1002/14651858.CD005496.pub4

47. Van den Akker C.H.P., van Goudoever J.B., Szajewska H., Embleton N.D., Hojsak I., Reid D., Shamir R. Probiotics for Preterm Infants: A Strain-Specific Systematic Review and Network Meta-analysis. J Pediatr Gastroenterol Nutr 2018; 67 (1): 103–122. DOI: 10.1097/mpg.0000000000001897.

48. Dani C., Biadaioli R., Bertini G., Martelli E., Rubaltelli F.F. Probiotics Feeding in Prevention of Urinary Tract Infection, Bacterial Sepsis and Necrotizing Enterocolitis in Preterm Infants. Neonatol 2002; 82(2); 103–108. DOI: 10.1159/000063096

49. Chrzanowska-Liszewska D., Seliga-Siwecka J., Kornacka M.K. The effect of Lactobacillus rhamnosus GG supplemented enteral feeding on the microbiotic flora of preterm infants-double blinded randomized control trial. Early Hum Dev 2012; 88(1): 57–60. DOI: 10.1016/j.earlhumdev.2011.07.002

50. Kane A.F., Bhatia A.D., Denning P.W., Shane A.L., Patel R.M. Routine Supplementation of Lactobacillus rhamnosus GG and Risk of Necrotizing Enterocolitis in Very Low Birth Weight Infants. J Pediatrics 2018; 195: 73–79. DOI: 10.1016/j.jpeds.2017.11.055

51. Patel S., Chaudhari M., Kadam S., Rao S., Patole S. Standardized feeding and probiotic supplementation for reducing necrotizing enterocolitis in preterm infants in a resource limited set up. Eur J Clin Nutr 2017; 72(2): 281–287. DOI: 10.1038/s41430-017-0040-7

52. Fang H.R., Zhang G.Q., Cheng J.Y., Li Z.Y. Efficacy of Lactobacillus-supplemented triple therapy for Helicobacter pylori infection in children: a meta-analysis of randomized controlled trials. Eur J Pediatr 2019; 178: 7–16. DOI: 10.1007/s00431-018-3282-z

53. Szajewska H., Albrecht P., Topczewska-Cabanek A. Randomized, double-blind, placebo-controlled trial: effect of lactobacillus GG supplementation on Helicobacter pylori eradication rates and side effects during treatment in children. J Pediatr Gastroenterol Nutr 2009; 48: 431–436. DOI: 10.1097/MPG.0b013e318182e716

54. Benninga M.A., Faure C., Hyman P.E., St James Roberts I., Schechter N.L., Nurko S. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterol 2016; 150: 1443. DOI: 10.1053/j.gastro. 2016.02.016

55. Partty A., Lehtonen L., Kalliomaki M., Salminen S., Isolauri E. Probiotic Lactobacillus rhamnosus GG therapy and microbiological programming in infantile colic: a randomized, controlled trial. Pediatr Res 2015; 78(4): 470–475. DOI: 10.1038/pr.2015.127

56. Cabana M.D., McKean M., Beck A.L., Flaherman V. Pilot analysis of early LGG for infant colic prevention. JPGN 2019; 68: 17–19. DOI: 10.1097/MPG.0000000000002113

57. Korterink J., Devanarayana N.M., Rajindrajith S., Vlieger A., Benninga M.A. Childhood functional abdominal pain: mechanisms and management. Nat Rev Gastroenterol Hepatol 2015; 12(3): 159–171. DOI: 10.1038/nrgastro.2015.21

58. Liu H.N., Wu H., Chen Y.Z., Chen Y.J., Shen X.Z., Liu T.T. Altered molecular signature of intestinal microbiota in irritable bowel syndrome patients compared with healthy controls: a systematic review and meta-analysis. Dig Liver Dis 2017; 49(4): 331–337. DOI: 10.1016/j.dld.2017.01.142

59. Horvath A., Dziechciarz P., Szajewska H. Meta-analysis: Lactobacillus rhamnosus GG for abdominal pain-related functional gastrointestinal disorders in childhood. Aliment Pharmacol Ther 2011; 33(12): 1302–1310. DOI: 10.1111/j.1365-2036.2011.04665.x

60. Hojsak I. Probiotics in Functional Gastrointestinal Disorders. Adv Exp Med Biol 2019; 1125: 121–137. DOI: 10.1007/5584_2018_321