ppharmПедиатрическая фармакологияPediatric pharmacology1727-57762500-3089Издательство «ПедиатрЪ»10.15690/pf.v10i2.644ppharm-235Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWТЕРАПЕВТИЧЕСКИЙ ПОТЕНЦИАЛ СОВРЕМЕННЫХ ПРОБИОТИКОВTHERAPEUTIC POTENTIAL OF MODERN PROBIOTICSУрсоваН. И.UrsovaN. I.

доктор медицинских наук, профессор, главный научный сотрудник педиатрического отделения МОНИКИ

ursovan@mail.ruМосковский областной научно-исследовательский клинический институт им. М.Ф. Владимирского, Российская ФедерацияРоссияVladimirsky Moscow Regional Clinical Research Institute, Russian FederationRussian Federation201301042013102Педиатрическая фармакология4656Copyright © Урсова Н.И., 20132013Урсова Н.И.Ursova N.I.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pedpharma.ru/jour/article/view/235

В дискуссионной статье приведен краткий обзор клинических исследований, при которых применение пробиотиков продемонстрировало лучшие результаты. Обсуждаются вопросы о способности пробиотиков оказывать протективное действие на кишечный барьер, антагонистическое ― на условно-патогенные микроорганизмы и стимулирующее ― на иммунитет. Рассматриваются наиболее изученные производственные виды и штаммы, входящие в состав пробиотических препаратов. Представлены различия между моноштаммовыми и мультивидовыми пробиотиками. Обосновывается целесообразность применения комбинированных препаратов с сочетанными аддитивными или синергическими штаммоспецифическими эффектами.

This discussion article adduces a short review of clinical studies where the use of probiotics has shown the best results. The issues of whether probiotics are capable of having a protective effect on the intestinal barrier, an antagonist effect – on opportunistic microbes and a stimulatory effect – on the immune system, are discussed. The best studied production species and strains forming probiotic drugs are observed. The differences between monostrain and multispecies probiotics are given. The reasonability of using combined drugs with combinational additive or synergetic strain-specific effects is explained.

пробиотикикишечный микробиоценозбифидобактериилактобациллымоноштаммовыемультиштаммовыемультивидовые препаратыprobioticsintestinal microbiocenosisbifidus bacterialactobacillimonostrainmultistrainmultispecies drugsReferencesШендеров Б. А. Медицинская микробная экология и функциональное питание. Пробиотики и функциональное питание. М.: Грантъ. 2001; 3: 286.Shenderov B.A. Meditsinskaya mikrobnaya ekologiya i funktsional'noe pitanie. Probiotiki i funktsional'noe pitanie [Medical Microbial Ecology and Functional Food. Probiotics and Functional Foods]. Moscow, Grant", 2001. 286 p.Szajewska H., Mrukowicz J. Probiotics in the treatment and prevention of acute infectious diarrhea in infants and children: a systematic review of published randomized, double-blind, placebo controlled trials. J Pediatr Gastroenterol Nutr. 2001; 33: 17–25.Szajewska H., Mrukowicz J. Probiotics in the treatment and prevention of acute infectious diarrhea in infants and children: a systematic review of published randomized, double-blind, placebo controlled trials. J Pediatr Gastroenterol Nutr. 2001; 33: 17–25.Bezkorovainy A. Probiotics: determinants of survival and growth in the gut. Am J Clin Nutr. 2001; 73: 399–405.Bezkorovainy A. Probiotics: determinants of survival and growth in the gut. Am J Clin Nutr. 2001; 73: 399–405.Бондаренко В. М. Фарматека. 2012; 13: 89–99.Bondarenko V.M. Farmateka - Pharmateca. 2012; 13: 89–99.Gorbach S. L. Probiotics and gastrointestinal health. Am G Gastroenterol. 2000; 95 (Suppl. 1): 2–4.Gorbach S. L. Probiotics and gastrointestinal health. Am G Gastroenterol. 2000; 95 (Suppl. 1): 2–4.Hunter J. O., Madden J. A. А review of the role of the gut microflora in irritable bowel syndrome and the effect of probiotics. Br J Nutr. 2002; 88 (Suppl. 1): 67–72.Hunter J. O., Madden J. A. А review of the role of the gut microflora in irritable bowel syndrome and the effect of probiotics. Br J Nutr. 2002; 88 (Suppl. 1): 67–72.Marteau P. R., de Vrese M., Cellier C. J., Schrezenmeir J. Protection from gastrointestinal diseases with use of probiotics. Am J Clin Nutr. 2001; 73 (Suppl. 2): 430–36.Marteau P. R., de Vrese M., Cellier C. J., Schrezenmeir J. Protection from gastrointestinal diseases with use of probiotics. Am J Clin Nutr. 2001; 73 (Suppl. 2): 430–36.Rolfe R. D. The role of probiotic cultures in the control of gastrointestinal health. J Nutr. 2000; 130 (Suppl. 2S): 396–402.Rolfe R. D. The role of probiotic cultures in the control of gastrointestinal health. J Nutr. 2000; 130 (Suppl. 2S): 396–402.Mercenier A., Pavan S., Pot B. Probiotics as biotherapeutic agent: present khuwledge and future prospects. Curr Pharm Des. 2003; 9: 175–91.Mercenier A., Pavan S., Pot B. Probiotics as biotherapeutic agent: present khuwledge and future prospects. Curr Pharm Des. 2003; 9: 175–91.Guidelines for the evaluation of probiotics in food: Joint FAO/WHO Working Group meeting. London, Ontario, Canada, 30 April — 1 May. 2002.Guidelines for the evaluation of probiotics in food: Joint FAO/WHO Working Group meeting. London, Ontario, Canada, 30 April — 1 May. 2002.Shida K., Nanno M. Probiotics and immunology: separating the wheat from the chaff. Trends Immynol. 2008; 29: 565–73.Shida K., Nanno M. Probiotics and immunology: separating the wheat from the chaff. Trends Immynol. 2008; 29: 565–73.Chapman T. M., Plosker G. L., Figgitt D. P. VSL#3 probiotic mixture: a review of its use in chronic inflammatory bowel diseases. Drugs. 2006; 66 (10): 1371–87.Chapman T. M., Plosker G. L., Figgitt D. P. VSL#3 probiotic mixture: a review of its use in chronic inflammatory bowel diseases. Drugs. 2006; 66 (10): 1371–87.Rachmilevitz D., Katakura K., Karmeli F. et al. Toll-like receptor 9 signaling mediates the anti-inflammatory effect of probiotics murine experimental colitis. Gastroenterol. 2004; 126 (2): 520–28.Rachmilevitz D., Katakura K., Karmeli F. et al. Toll-like receptor 9 signaling mediates the anti-inflammatory effect of Probiotics murine experimental colitis. Gastroenterol. 2004; 126 (2): 520–28.Bergonzelli G. E., Blum S., Brussow H. et al. Probiotics as a treatment strategy for gastrountestinal diseases? Digestion. 2005; 72: 57–68.Bergonzelli G. E., Blum S., Brussow H. et al. Probiotics as a treatment strategy for gastrountestinal diseases? Digestion. 2005; 72: 57–68.Penner R., Fedorak R. N., Madsen K. L. Probiotics and nutraceuticals: non-medicinal treatments of gastrointestinal diseases. Curr Opin Pharmacol. 2005; 5: 596–603.Penner R., Fedorak R. N., Madsen K. L. Probiotics and nutraceuticals: non-medicinal treatments of gastrointestinal diseases. Curr Opin Pharmacol. 2005; 5: 596–603.Ghadimi D., Folster-Holst R. Effects of probiotic bacteria and their genomic DNA on TH1/TH2-cytokine production by peripheral blood mononuclear cells (PBMCs) of healthy and allergic subjects. Immunobiology. 2008; 213: 677–92.Ghadimi D., Folster-Holst R. Effects of probiotic bacteria and their genomic DNA on TH1/TH2-cytokine production by peripheral blood mononuclear cells (PBMCs) of healthy and allergic subjects. Immunobiology. 2008; 213: 677–92.Metchnikoff E. The prolongation of life. Optimistic studies. London, United Kingdom: William Heinemann. 1907.Metchnikoff E. The prolongation of life. Optimistic studies. London, United Kingdom: William Heinemann. 1907.Reid G. Regulatory and clinical aspects of dairy probiotics. FAO/WHO Expert consultation on evalution of health and nutritional properties of powder milk with live lactic acid bacteria. Cordoba, Argentina. 2001. Р. 1–34.Reid G. Regulatory and clinical aspects of dairy probiotics. FAO/WHO Expert consultation on evalution of health and nutritional properties of powder milk with live lactic acid bacteria. Cordoba, Argentina, 2001. pp. 1–34.FAO/WHO. The food and agriculture organization of the United Nations and the World Health Organization Joint FAO/WHO expert consultation on evalution of health and nutritional propecties of probiotics in food including powder milk with live lactic acid bacteria. 2001 (10–1).FAO/WHO. The food and agriculture organization of the United Nations and the World Health Organization Joint FAO/WHO expert consultation on evalution of health and nutritional propecties of probiotics in food including powder milk with live lactic acid bacteria. 2001 (10–1).Timmerman H. M., Koning C. J. M., Mulder L., Rombouts F. M., Beynen A. C. Monostrain, multistrain and multispecies probiotics. A comparison of functionality and efficacy. Int J Food Microbiol. 2004; 96: 219–33.Timmerman H. M., Koning C. J. M., Mulder L., Rombouts F. M., Beynen A. C. Monostrain, multistrain and multispecies probiotics. A comparison of functionality and efficacy. Int J Food Microbiol. 2004; 96: 219–33.Salminen S., Isolauri E., Onela T. Gut flora in normal and disordered states. Chemotherapy. 1995; 41 (Suppl. 1): 5–15.Salminen S., Isolauri E., Onela T. Gut flora in normal and disordered states. Chemotherapy. 1995; 41 (Suppl. 1): 5–15.Van der Waaij D. Colonization resistance of the Digestive Tract. Japan. 1999. Р. 76–81.Van der Waaij D. Colonization resistance of the Digestive Tract. Japan. 1999. Р. 76–81.Постникова Е. А., Пикина А. П., Кафарская Л. И., Ефимов Б. А. Журн. микробиол. 2004; 1: 67–69.Postnikova E.A., Pikina A.P., Kafarskaya L.I., Efimov B.A. Zhurn. mikrobiol – Journal of microbiology. 2004; 1: 67–69.Fons M., Gomez A., Karjalainen T. Mechanisms of colonization and colonization resistance of the digestive tract. Microbial Ecol Health Dis Sup. 2000; 2: 240–6.Fons M., Gomez A., Karjalainen T. Mechanisms of colonization and colonization resistance of the digestive tract. Microbial Ecol Health Dis Sup. 2000; 2: 240–6.Bry L., Falk P. G., Midtvedt T., Gordon J. I. A model of hostmicrobial interactions in an open mammalian ecosystem. Science. 1996; 273 (5280): 1380–3.Bry L., Falk P. G., Midtvedt T., Gordon J. I. A model of hostmicrobial interactions in an open mammalian ecosystem. Science. 1996; 273 (5280): 1380–3.Hooper L. V., Xu J., Falk P. G., Midtvedt T., Gordon J. I. A molecular sensor that allows a gut commensal to control its nutrient foundation in a competitive ecosystem. Proc Natl Acad Sci. USA. 1999; 96 (17): 9833–8.Hooper L. V., Xu J., Falk P. G., Midtvedt T., Gordon J. I. A molecular sensor that allows a gut commensal to control its nutrient foundation in a competitive ecosystem. Proc Natl Acad Sci. USA. 1999; 96 (17): 9833–8.Mowat A. M. Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol. 2003; 3 (4): 331–41.Mowat A. M. Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol. 2003; 3 (4): 331–41.Kelly D., Conway S., Aminov R. Commensal gut bacteria: mechanisms of immune modulation. Trends Immunol. 2005; 26 (6): 326–33.Kelly D., Conway S., Aminov R. Commensal gut bacteria: mechanisms of immune modulation. Trends Immunol. 2005; 26 (6): 326–33.Mayer L., Shao L. Therapeutic potential of oral tolerance. Nat Rev Immunol. 2004; 4 (6): 407–19.Mayer L., Shao L. Therapeutic potential of oral tolerance. Nat Rev Immunol. 2004; 4 (6): 407–19.Hawrylowicz C. M., O'Garra A. Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Nat Rev Immunol. 2005; 5 (4): 271–83.Hawrylowicz C. M., O'Garra A. Potential role of interleukin- 10-secreting regulatory T cells in allergy and asthma. Nat Rev Immunol. 2005; 5 (4): 271–83.Kapsenberg M. L. Dendritic-cell control of pathogen-driven T-cell polarization. Nat Rev Immunol. 2003; 3 (12): 984–93.Kapsenberg M. L. Dendritic-cell control of pathogen-driven T-cell polarization. Nat Rev Immunol. 2003; 3 (12): 984–93.Holzapfel W. H., Haberer P., Geisen R. et al. Taxonomy and important features of probiotic microorganisms in food and nutrition. Am J Clin Nutr. 2001; 73: 365–73.Holzapfel W. H., Haberer P., Geisen R. et al. Taxonomy and important features of probiotic microorganisms in food and nutrition. Am J Clin Nutr. 2001; 73: 365–73.Lee Y. K., Lim C. Y., Teng W. L. et al. Quantitative approach in the study of adhesion of lactic acid bacteria to intestinal cells ant their competition with enterobacteria. Appl Envir Microbiol. 2000; 66 (9): 3692–97.Lee Y. K., Lim C. Y., Teng W. L. et al. Quantitative approach in the study of adhesion of lactic acid bacteria to intestinal cells ant their competition with enterobacteria. Appl Envir Microbiol. 2000; 66 (9): 3692–97.O'Sullivan D. J. Screening of intestinal microflora for effective probiotic bacteria. J Ag Food Chem. 2001; 49: 1751–60.O'Sullivan D. J. Screening of intestinal microflora for effective probiotic bacteria. J Ag Food Chem. 2001; 49: 1751–60.Schell M. A., Karmirantzou M., Snel B. et al. The genome sequence of Bifidobacterium longum reflect its adaptation to the human gastrointestinal tract. Proc Natl Sci. USA. 2002; 99 (22): 14422–27.Schell M. A., Karmirantzou M., Snel B. et al. The genome sequence of Bifidobacterium longum reflect its adaptation to the human gastrointestinal tract. Proc Natl Sci. USA. 2002; 99 (22): 14422–27.Tannock G. W. Molecular assessment of intestinal microflora. Am J Clin Nutr. 2001; 73: 410–14.Tannock G. W. Molecular assessment of intestinal microflora. Am J Clin Nutr. 2001; 73: 410–14.Resta-Lenert S., Barrett K. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli. Gut. 2003; 52: 988–997.Resta-Lenert S., Barrett K. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli. Gut. 2003; 52: 988–997.Putaala H., Salusjarvi T. Effect of four probiotic strains and Echerichia coli O157: H7 on tight junction integrity and cyclooxygenase expression. Res Microbiol. 2008. Doi:10.1016/ j.resmic.2008.08.002.Putaala H., Salusjarvi T. Effect of four probiotic strains and Echerichia coli O157: H7 on tight junction integrity and cyclooxygenase expression. Res Microbiol. 2008. Doi:10.1016/Gill H. S. Probiotic to enhance anti-infective defenses in the gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2003; 17: 755–73.j.resmic.2008.08.002.Oksaharju A., Kankainen M., Kekkonen R. A. et al. Probiotic Lactobacillus rhamnosus downregulates FCER1 and HRH4 expression in human mast cell. World J Gastroenterol. 2011; 17: 750–9.Gill H. S. Probiotic to enhance anti-infective defenses in the gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2003; 17: 755–73.Alakomi H. L., Skytta E., Saarela M. et al. Lactic acid permebilizes gram-negative bacteria by disrupting the outer membrane. Applied Environ Microbiol. 2000; 66: 2001–5.Oksaharju A., Kankainen M., Kekkonen R. A. et al. Probiotic Lactobacillus rhamnosus downregulates FCER1 and HRH4 expression in human mast cell. World J Gastroenterol. 2011; 17: 750–9.Pan X., Chen F., Wu T. et al. The acid, bile tolerance and antimicrobial property of Lactobacillus acidophilus NIT. Food Control. 2008. Doi:10.1016/j.foodcont.2008.08.019.Alakomi H. L., Skytta E., Saarela M. et al. Lactic acid permebilizes gram-negative bacteria by disrupting the outer membrane. Applied Environ Microbiol. 2000; 66: 2001–5.Salminen S., Salminen E. Lactulose lactic acid bacteria intestinal microecology and mucosal protection. Scand J Gastroenterol. 1997; 222: 45–8.Pan X., Chen F., Wu T. et al. The acid, bile tolerance and antimicrobial property of Lactobacillus acidophilus NIT. Food Control. 2008. Doi:10.1016/j.foodcont.2008.08.019.Lanning D. K., Rhee K. J., Knight K. L. Intestinal bacteria and development of the B-lymphocyte repertoire. Trends Immunol. 2005; 26 (8): 419–25.Salminen S., Salminen E. Lactulose lactic acid bacteria intestinal microecology and mucosal protection. Scand J Gastroenterol. 1997; 222: 45–8.Cotter P. D., Hill C., Ross R. P. Developing innate immunity for food. Nat Rev Microbiol. 2005; 3: 777–88.Lanning D. K., Rhee K. J., Knight K. L. Intestinal bacteria and development of the B-lymphocyte repertoire. Trends Immunol. 2005; 26 (8): 419–25.Strompfova V., Laukova A. In vitro study on bacteriocin production of Enterococci associated with chickens. Anaerobe. 2007; 13: 228–37.Cotter P. D., Hill C., Ross R. P. Developing innate immunity for food. Nat Rev Microbiol. 2005; 3: 777–88.Chavez A. M., Menconi M. J., Hodin R. A. et al. Cytokineinduced intestinal epithelial hyperpermeability: role of nitric oxide. Crit Care Med. 1999; 27: 2246–51.Strompfova V., Laukova A. In vitro study on bacteriocin production of Enterococci associated with chickens. Anaerobe. 2007; 13: 228–37.Sobko T., Reinders C. L., Jansson E. A. et al. Gastrointestinal bacteria generate nitric oxide from nitrate and nitrite. Nitric Oxide. 2005; 13: 163–69.Chavez A. M., Menconi M. J., Hodin R. A. et al. Cytokineinduced intestinal epithelial hyperpermeability: role of nitric oxide. Crit Care Med. 1999; 27: 2246–51.Lundberg J. O., Weitzberg E., Cole J. A. et al. Nitrate, bacteria and human health. Nat Rev Microbiol. 2004; 2: 593–602.Sobko T., Reinders C. L., Jansson E. A. et al. Gastrointestinal bacteria generate nitric oxide from nitrate and nitrite. Nitric Oxide. 2005; 13: 163–69.Lu L., Walker A. Pathologic and physiologic interactions of bacteria with the gastrointestinal epithelium. Am J Clin Nutr. 2001; 73: 1124–30.Lundberg J. O., Weitzberg E., Cole J. A. et al. Nitrate, bacteria and human health. Nat Rev Microbiol. 2004; 2: 593–602.Lebeer S., Vanderleydes G., De Keersmaecker S. C. Genes and molecules of lactobacillus supporting probiotic action. Microbiol Mol Biol Rev. 2008; 72: 728–64.Lu L., Walker A. Pathologic and physiologic interactions of bacteria with the gastrointestinal epithelium. Am J Clin Nutr. 2001; 73: 1124–30.Perdigon G., Fuller R., Raya R. Lactis acid bacteria and their effect on the immune system. Curr Issues Intest Microbiol. 2001; 2 (1): 27–42.Lebeer S., Vanderleydes G., De Keersmaecker S. C. Genes and molecules of lactobacillus supporting probiotic action. Microbiol Mol Biol Rev. 2008; 72: 728–64.Лиходед В. Г., Бондаренко В. М. Антиэндотоксиновый иммунитет в регуляции численности микрофлоры кишечника. М.: Медицина. 2007. 216 с.Perdigon G., Fuller R., Raya R. Lactis acid bacteria and their effect on the immune system. Curr Issues Intest Microbiol. 2001; 2 (1): 27–42.Vinderola G., Matar C., Perdigon G. Role of intestinal epithelial cells in immune effects mediated by gram-positive probiotic bacteria: involvement of toll-like receptors. Clin Diagn Lab Immunol. 2005; 12 (9): 1075–84.Likhoded V.G., Bondarenko V.M. Antiendotoksinovyi immunitet v regulyatsii chislennosti mikroflory kishechnika [Endotoxin Immunity in the Regulation of the Microflora Size of the Intestinal]. Moscow, Meditsina, 2007. 216 p.Isolauri E., Juntunen M., Rautanen T. et al. A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children. Pediatrics. 1991; 88: 90–7.Vinderola G., Matar C., Perdigon G. Role of intestinal epithelial cells in immune effects mediated by gram-positive probiotic bacteria: involvement of toll-like receptors. Clin Diagn Lab Immunol. 2005; 12 (9): 1075–84.Isolauri E., Salminen S., Ouwehand A. C. Microbial-gut interactions in health and disease. Probiotics. Best Pract Res Clin Gastroenterol. 2004; 18: 299–313.Isolauri E., Juntunen M., Rautanen T. et al. A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children. Pediatrics. 1991; 88: 90–97.Isolauri E., Kirjavainen P. V., Salminen S. Probiotics: role in the treatment of intestinal infection and inflammation. Gut. 2002; 50 (3): 154–59.Isolauri E., Salminen S., Ouwehand A. C. Microbial-gut interactions in health and disease. Probiotics. Best Pract Res Clin Gastroenterol. 2004; 18: 299–313.Walker W. A., Goulet O., Morelli L. et al. Progress in the science of probiotics: from cellular microbiology and applied immunology to clinical nutrition. Eur J Nutr. 2006; 45: 1–18.Isolauri E., Kirjavainen P. V., Salminen S. Probiotics: role in the treatment of intestinal infection and inflammation. Gut. 2002; 50 (3): 154–59.Бондаренко В. М. Фарматека. 2010; 2: 26–32.Walker W. A., Goulet O., Morelli L. et al. Progress in the science of probiotics: from cellular microbiology and applied immunology to clinical nutrition. Eur J Nutr. 2006; 45: 1–18.Allen S. J., Okoko B., Martinez E., Gregorio G., Dans L. F. Probiotics for treating infectious diarrhea. Cochrane Database Syst Rev. 2004; 2: CD003048.Bondarenko V.M. Farmateka - Pharmateca. 2010; 2: 26–32.Lee M. C., Lin L. H., Hung K. L., Wu H. Y. Oral bacterial therapy promotes recovery from acute diarrhea in children. Acta Paediatr. Taiwan. 2001; 42: 301–5.Allen S. J., Okoko B., Martinez E., Gregorio G., Dans L. F. Probiotics for treating infectious diarrhea. Cochrane Database Syst Rev. 2004; 2: CD003048.Sazawal S., Hiremath G., Dhingra U. et al. Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials. Lancet Infect Dis. 2006; 6: 474–82.Lee M. C., Lin L. H., Hung K. L., Wu H. Y. Oral bacterial therapy promotes recovery from acute diarrhea in children. Acta Paediatr. Taiwan. 2001; 42: 301–5.Hickson M., D'Souza A. L., Muthu N. et al. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ. 2007; 335 (7610): 80.Sazawal S., Hiremath G., Dhingra U. et al. Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials. Lancet Infect Dis. 2006; 6: 474–82.Nista E. C., Candelli M., Cremonini F. et al. Bacillus clausii therapy to reduce side-effects of anti-Helicobacter pylori treatment: randomized, double-blind, placebo controlled trial. Aliment Pharmacol Ther. 2004; 20: 1181–8.Hickson M., D'Souza A. L., Muthu N. et al. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ. 2007; 335 (7610): 80.Beausoleil M., Fortier N., Guenette S. et al. Effect of a fermented milk combining Lactobacillus acidophilus C11285 and Lactobacillus casei in the prevention of antibiotic-associated diarrhea: a randomized, double-blind, placebo-controlled trial. Can J Gastroenterol. 2007; 21: 732–6.Nista E. C., Candelli M., Cremonini F. et al. Bacillus clausii therapy to reduce side-effects of anti-Helicobacter pylori treatment: randomized, double-blind, placebo controlled trial. Aliment Pharmacol Ther. 2004; 20: 1181–8.Plummer S., Weaver M. A., Harris J. C. et al. Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of Clostridium difficile diarrhea. Int Microbiol. 2004; 7: 59–62.Beausoleil M., Fortier N., Guenette S. et al. Effect of a fermented milk combining Lactobacillus acidophilus C11285 and Lactobacillus casei in the prevention of antibiotic-associated diarrhea: a randomized, double-blind, placebo-controlled trial. Can J Gastroenterol. 2007; 21: 732–6.Tong J. L., Ran Z. H., Shen J. et al. Meta-analysis: the effect of supplementation with probiotics on eradication rates and adverse events during Helicobacter pylori eradication therapy. Aliment Pharmacol Ther. 2007; 25: 155–68.Plummer S., Weaver M. A., Harris J. C. et al. Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of Clostridium difficile diarrhea. Int Microbiol. 2004; 7: 59–62.Sykora J., Valeckova K., Amlerova J. et al. Effects of a specially designed fermented milk product containing probiotic Lactobacillus casei DN-114 001 and the eradication Helicobacter pylori in children:prospective randomized double-blind study. J Clin Gastroenterol. 2005; 39: 692–8.Tong J. L., Ran Z. H., Shen J. et al. Meta-analysis: the effect of supplementation with probiotics on eradication rates and adverse events during Helicobacter pylori eradication therapy. Aliment Pharmacol Ther. 2007; 25: 155–68.O'Mahony L., McCarthy J., Kelly P. et al. Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005; 128: 541–51.Sykora J., Valeckova K., Amlerova J. et al. Effects of a specially designed fermented milk product containing probiotic Lactobacillus casei DN-114 001 and the eradication Helicobacter pylori in children: prospective randomized double-blind study. J Clin Gastroenterol. 2005; 39: 692–8.Gawronska A., Dziechciarz P., Horvath A., Szajewska H. A randomized double-blind placebo-controlled trial of Lactobacillus GG for abdominal pain disorders in children. Aliment Pharmacol Ther. 2007; 25: 177–84.O'Mahony L., McCarthy J., Kelly P. et al. Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005; 128: 541–51.Gawronska A., Dziechciarz P., Horvath A., Szajewska H. A randomized double-blind placebo-controlled trial of Lactobacillus GG for abdominal pain disorders in children. Aliment Pharmacol Ther. 2007; 25: 177–84.Gawronska A., Dziechciarz P., Horvath A., Szajewska H. A randomized double-blind placebo-controlled trial of Lactobacillus GG for abdominal pain disorders in children. Aliment Pharmacol Ther. 2007; 25: 177–84.Kim H. J., Vazquez Roque M. I., Camilleri M. et al. A randomized controlled trial of a probiotic combination VSL#3 and placebo in irritable bowel syndrome with bloating. Neurogastroenterol Motil. 2005; 17: 687–96.Kim H. J., Vazquez Roque M. I., Camilleri M. et al. A randomized controlled trial of a probiotic combination VSL#3 and placebo in irritable bowel syndrome with bloating. Neurogastroenterol Motil. 2005; 17: 687–96.Kajander K., Hatakka K., Poussa T., Farkkila M., Korpela R. A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6-month intervention. Aliment Pharmacol Ther. 2005; 22: 387–94.Kajander K., Hatakka K., Poussa T., Farkkila M., Korpela R. A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6-month intervention. Aliment Pharmacol Ther. 2005; 22: 387–94.Guyonnet D., Chassany O., Ducrotte P. et al. Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind, controlled trial. Aliment Pharmacol Ther. 2007; 26: 475–86.Guyonnet D., Chassany O., Ducrotte P. et al. Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind, controlled trial. Aliment Pharmacol Ther. 2007; 26: 475–86.Kruis W., Fric P., Pokrotnieks J. et al. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut. 2004; 53: 1617–23.Kruis W., Fric P., Pokrotnieks J. et al. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut. 2004; 53: 1617–23.Rayes N., Seehofer D., Theruvath T. et al. Supply of preand probiotics reduces bacterial infection rates after liver transplantation — a randomized, double-blind trial. Am J Transplant. 2005; 5: 125–30.Rayes N., Seehofer D., Theruvath T. et al. Supply of preand probiotics reduces bacterial infection rates after liver transplantation — a randomized, double-blind trial. Am J Transplant. 2005; 5: 125–30.Darmov I.V., Chicherin I.Yu., Pogorel'skii I.P., Lundovskikh I.A. Eksperiment. i klin. gastroenterologiya – Experimental and clinical gastroenterology. 2011; 3: 6–11.Darmov I.V., Chicherin I.Yu., Pogorel'skii I.P., Lundovskikh I.A. Eksperiment. i klin. gastroenterologiya – Experimental and clinical gastroenterology. 2011; 3: 6–11.Darmov I.V., Chicherin I.Yu., Erdyakova A.S., Pogorel'skii I.P., Lundovskikh I.A. Kishechnaya mikroflora - Intestinal microflora. 2012; 1: 11–15.Darmov I.V., Chicherin I.Yu., Erdyakova A.S., Pogorel'skii I.P., Lundovskikh I.A. Kishechnaya mikroflora - Intestinal microflora. 2012; 1: 11–15.Deshpande G., Rao S., Patole S. Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: a systematic review of randomised controlled trials.Deshpande G., Rao S., Patole S. Probiotics for prevention of necrotising enterocolitis in preterm neonates with very low birthweight: a systematic review of randomised controlled trials.Lancet. 2007; 369: 1614–20.Lancet. 2007; 369: 1614–20.Botina S.G., Ivashkina N.Yu., Maev I.V. Molekulyarnaya meditsina – Molecular medicine. 2011; 2: 53–57.Botina S.G., Ivashkina N.Yu., Maev I.V. Molekulyarnaya meditsina – Molecular medicine. 2011; 2: 53–57.Kankainen M., Paulin L., Tynkkynen S. et al. Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pill containing a human mucus binding protein. Proc Natl Acad Sci. USA. 2009; 106 (40): 17193–98.Kankainen M., Paulin L., Tynkkynen S. et al. Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pill containing a human mucus binding protein. Proc Natl Acad Sci. USA. 2009; 106 (40): 17193–98.Darmov I.V., Chicherin I.Yu., Pogorel'skii I.P., Lundovskikh I.A., Durnev E.A. Zhurn. infektol. – Journal of infectology. 2012; 4 (1): 68–74.Darmov I.V., Chicherin I.Yu., Pogorel'skii I.P., Lundovskikh I.A., Durnev E.A. Zhurn. infektol. – Journal of infectology. 2012; 4 (1): 68–74.World Gastroenterology Organization practice guideline: Probiotics and prebiotics. Arab J Gastroenterology. 2009; 10 (1): 33–42.World Gastroenterology Organization practice guideline: Probiotics and prebiotics. Arab J Gastroenterology. 2009; 10 (1): 33–42.Chicherin I.Yu., Darmov I.V., Bogacheva N.V. et al. Kishechnaya mikroflora. Sbornik nauchnykh statei - Intestinal microflora. Collection of papers. 2012; 1: 24–29.Chicherin I.Yu., Darmov I.V., Bogacheva N.V. et al. Kishechnaya mikroflora. Sbornik nauchnykh statei - Intestinal microflora. Collection of papers. 2012; 1: 24–29.Erdyakova A.S., Chicherin I.Yu., Lundovskikh I.A., Pogorel'skii I.P. Kishechnaya mikroflora. Sbornik nauchnykh statei - Intestinal microflora. Collection of papers. 2012; 1: 21–23.Erdyakova A.S., Chicherin I.Yu., Lundovskikh I.A., Pogorel'skii I.P. Kishechnaya mikroflora. Sbornik nauchnykh statei - Intestinal microflora. Collection of papers. 2012; 1: 21–23.Marteau P., Shanahan F. Basic aspects and pharmacology of probiotics — an overview on pharmacokinetics, mechanisms of action and side effects. Best Pract Res Clin Gastroenterol.Marteau P., Shanahan F. Basic aspects and pharmacology of probiotics — an overview on pharmacokinetics, mechanisms of action and side effects. Best Pract Res Clin Gastroenterol.; 17 (5): 725–40.; 17 (5): 725–40.Doronin A.F., Shenderov B.A. Funktsional'noe pitanie [Functional Nutrition]. M.osocw, Grant", 2002. 296 p.Doronin A.F., Shenderov B.A. Funktsional'noe pitanie [Functional Nutrition]. M.osocw, Grant", 2002. 296 p.Chicherin I.Yu., Darmov I.V., Pogorel'skii I.P. et al. Kishechnaya mikroflora - Intestinal microflora. 2012; 1: 35–40.Chicherin I.Yu., Darmov I.V., Pogorel'skii I.P. et al. Kishechnaya mikroflora - Intestinal microflora. 2012; 1: 35–40.Famularo G., Di Simone C., Matteuzzi D., Pirovano F. Traditional and high potency probiotic preparations for oral bacteriotherapy. Biodrigs. 1999; 12: 544–70.Famularo G., Di Simone C., Matteuzzi D., Pirovano F. Traditional and high potency probiotic preparations for oral bacteriotherapy. Biodrigs. 1999; 12: 544–70.Sanders M. E., Huis in't Veld J. Bringing a probiotic-containing functional food to the market: microbiological, product, regulatory and labeling issues. Antonie Van Leeuwenhoek. 1999; 76: 293–315.Sanders M. E., Huis in't Veld J. Bringing a probiotic-containing functional food to the market: microbiological, product, regulatory and labeling issues. Antonie Van Leeuwenhoek. 1999; 76: 293–315.Dunne C., Murphy L., Flynn S., O'Mahony L., O'Halloran. et al. Probiotics: from myth to reality. Demonstration of functionality in animal models of disease and in human clinical trials. Antonie Van Leeuwenhoek. 1999; 76: 279–92.Dunne C., Murphy L., Flynn S., O'Mahony L., O'Halloran. et al. Probiotics: from myth to reality. Demonstration of functionality in animal models of disease and in human clinical trials. Antonie Van Leeuwenhoek. 1999; 76: 279–92.Zoppi G., Cinquetti M., Benini A., Bonamini E., Minelli E. Modulation of the intestinal ecosystem by probiotics and lactulose in children during treatment with ceftriaxone. Curr Therap Res. 2001; 62: 418–35.Zoppi G., Cinquetti M., Benini A., Bonamini E., Minelli E. Modulation of the intestinal ecosystem by probiotics and lactulose in children during treatment with ceftriaxone. Curr Therap Res. 2001; 62: 418–35.Shibolet O., Karmeli F., Eliakim R. et al. Variable response to probiotics in two models of experimental colitis in rats. Inflamm Bowel Dis. 2002; 8: 399–406.Shibolet O., Karmeli F., Eliakim R. et al. Variable response to probiotics in two models of experimental colitis in rats. Inflamm Bowel Dis. 2002; 8: 399–406.Ullisse S., Gionchetti P., D'Alo S. et al. Expression of cytokines, inducible nitric oxide synthase, and matrix metalloproteinases in pouchitis; effects of probiotic treatment. Am J Gastroenterol. 2001; 96: 2691–9.Ullisse S., Gionchetti P., D'Alo S. et al. Expression of cytokines, inducible nitric oxide synthase, and matrix metalloproteinases in pouchitis; effects of probiotic treatment. Am J Gastroenterol. 2001; 96: 2691–9.Perdigon G., Nader de Macias Ms E., Alvarez S. et al. Prevention of gastrointestinal infection usingimmunobiological methods with milk fermented with Lactobacillus casei and Lactobacillus acidophilus. J Dairy Res. 1990; 57: 255–64.Perdigon G., Nader de Macias Ms E., Alvarez S. et al. Prevention of gastrointestinal infection usingimmunobiological methods with milk fermented with Lactobacillus casei and Lactobacillus acidophilus. J Dairy Res. 1990; 57: 255–64.Lema M., William L., Rao D. R. Reduction of faecal shedding of enterohemorragic Escherichia coli O157: H7 in lambs by feeding microbial feed supplement. Small Rumin Res. 2001; 39: 31–9.Lema M., William L., Rao D. R. Reduction of faecal shedding of enterohemorragic Escherichia coli O157: H7 in lambs by feeding microbial feed supplement. Small Rumin Res. 2001; 39: 31–9.van Es M., Timmerman H. M. Onderzoek naar multispecies probiotica voor niet-humane toepassingen. BTS-project 98186. 2002.van Es M., Timmerman H. M. Onderzoek naar multispecies probiotica voor niet-humane toepassingen. BTS-project 98186. 2002.Gill H. S., Shu Q., Lin H., Rutherfurd K. J., Cross M. L. Protection against translocating Salmonella typhimurium infection in mice by feeding the immuno-enhancing probiotic Lactobacillus rhamnosus strain HNOO1. Med Microbiol Immunol. 2001; 190: 97–104.Gill H. S., Shu Q., Lin H., Rutherfurd K. J., Cross M. L. Protection against translocating Salmonella typhimurium infection in mice by feeding the immuno-enhancing probiotic Lactobacillus rhamnosus strain HNOO1. Med Microbiol Immunol. 2001; 190: 97–104.Frolich-Wyder M. T., Bachmann H. P., Casey M. G. Interactions between propionibacteria and starter/nonstarter lactic acid bacteria in Swiss-type cheese. Lait. 2002; 82: 1–15.Frolich-Wyder M. T., Bachmann H. P., Casey M. G. Interactions between propionibacteria and starter/nonstarter lactic acid bacteria in Swiss-type cheese. Lait. 2002; 82: 1–15.Shankar P., Davies F. Associated bacterial growth in yogurt starters, initial abservation on stimulatory factors. J Soc Dairy Technol. 1976; 30: 31–2.Shankar P., Davies F. Associated bacterial growth in yogurt starters, initial abservation on stimulatory factors. J Soc Dairy Technol. 1976; 30: 31–2.Ouwehand A. C., Isolauri E., Kirjavainen P. V. et al. The mucus binding of B. lactis Bb12 is enhanced in the presence of LGG and L. delbrueckii subsp. Bulgaricus. Lett Appl Microbiol. 2000; 30: 10–3.Ouwehand A. C., Isolauri E., Kirjavainen P. V. et al. The mucus binding of B. lactis Bb12 is enhanced in the presence of LGG and L. delbrueckii subsp. Bulgaricus. Lett Appl Microbiol. 2000; 30: 10–3.Ouwehand A. C., Suomalainen T., Tolkko S., Salminen S. In vitro adhesion of propionoc acid bacteria to human intestinal mucus. Lait. 2002; 82: 123–30.Ouwehand A. C., Suomalainen T., Tolkko S., Salminen S. In vitro adhesion of propionoc acid bacteria to human intestinal mucus. Lait. 2002; 82: 123–30.Yuldasheva D.Kh., Kamilova A.T. Voprosy detskoi dietologii - Problems of pediatric nutritiology.. 2012; 10 (2): 50–52.Yuldasheva D.Kh., Kamilova A.T. Voprosy detskoi dietologii - Problems of pediatric nutritiology.. 2012; 10 (2): 50–52.Yuldasheva D.Kh., Kamilova A.T. Aktual'nye problemy abdominal'noi patologii u detei [Actual Problems of Abdominal Pathology in Children]. Moscow, 2010. pp. 163–164.Yuldasheva D.Kh., Kamilova A.T. Aktual'nye problemy abdominal'noi patologii u detei [Actual Problems of Abdominal Pathology in Children]. Moscow, 2010. pp. 163–164.Walter J. Ecological role of lactobacilli in the gastrointestinal tract: implication for fundamental and biomedical research. Appl Envir Microbiol. 2008; 74 (16): 4985–96.Walter J. Ecological role of lactobacilli in the gastrointestinal tract: implication for fundamental and biomedical research. Appl Envir Microbiol. 2008; 74 (16): 4985–96.Broad A., Jones D. E., Kirby J. A. Toll-like receptor (TLR) response tolerance: a key physiological «damage limitation» effect and an important potential opportunity for therapy. Curr Med Chem. 2006; 13 (21): 2487–502.Broad A., Jones D. E., Kirby J. A. Toll-like receptor (TLR) response tolerance: a key physiological «damage limitation» effect and an important potential opportunity for therapy. Curr Med Chem. 2006; 13 (21): 2487–502.Vinderola G., Matar C., Perdigon G. Role of intestinal epithelial cells in immune effects mediated by gram-positive probiotic bacteria: involvement of toll-like receptors. Clin Diagn Lab Immunol. 2005; 12 (9): 1075–84.Vinderola G., Matar C., Perdigon G. Role of intestinal epithelial cells in immune effects mediated by gram-positive probiotic bacteria: involvement of toll-like receptors. Clin Diagn Lab Immunol. 2005; 12 (9): 1075–84.Driessen F. M., Kingma F., Stadhouder J. Evidence that Lactobacillus bulgaricusin yoghurt is stimulated by carbon dioxide produced by Streptococcus thermophiles. Neth Milk Dairy J. 1982; 36: 135–44.Driessen F. M., Kingma F., Stadhouder J. Evidence that Lactobacillus bulgaricusin yoghurt is stimulated by carbon dioxide produced by Streptococcus thermophiles. Neth Milk Dairy J. 1982; 36: 135–44.Gomes A. M., Malcata F. X., Klaver F. A. Growth enhance ment of Bifidobacterium lactis and Lactobacillus acidophilus Ki by milk hydrolyzates. J Dairy Sci. 1998; 81: 2817–25.Gomes A. M., Malcata F. X., Klaver F. A. Growth enhance ment of Bifidobacterium lactis and Lactobacillus acidophilus Ki by milk hydrolyzates. J Dairy Sci. 1998; 81: 2817–25.Kailasapathy K., Chin J. Survival and therapeutic potential of probiotic organisms with reference to Lactobacillus acidophilus and Bifidobacterium spp. Immunol Cell Biol. 2000; 78: 80–8.Kailasapathy K., Chin J. Survival and therapeutic potential of probiotic organisms with reference to Lactobacillus acidophilus and Bifidobacterium spp. Immunol Cell Biol. 2000; 78: 80–8.Tokareva N. Gastroenterologiya = Gastroenterology. 2011; 3: 77–84.Tokareva N. Gastroenterologiya = Gastroenterology. 2011; 3: 77–84.Chicherin IYu., Pogorel'skii I.P., Darmov I.V. et al. Prakticheskaya meditsina = Practical medicine. 2012; 3: 47–55.Chicherin IYu., Pogorel'skii I.P., Darmov I.V. et al. Prakticheskaya meditsina = Practical medicine. 2012; 3: 47–55.

The authors declare that there are no conflicts of interest present.