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Захарова И.Н., Лаврова Т.Е., Талызина М.Ф., Мачнева Е.Б. Новый взгляд на пребиотики: гипотезы, тенденции, доказательства. Педиатрия (Прил. к журн. Consilium Medicum). 2017; 3: 26–33.
________________________________________________
Zakharova I.N., Lavrova T.E., Talyzina M.F., Machneva E.B. A new look at prebiotics: hypotheses, trends, evidence. Pediatrics (Suppl. Consilium Medicum). 2017; 3: 26–33.
Новый взгляд на пребиотики: гипотезы, тенденции, доказательства
Захарова И.Н., Лаврова Т.Е., Талызина М.Ф., Мачнева Е.Б. Новый взгляд на пребиотики: гипотезы, тенденции, доказательства. Педиатрия (Прил. к журн. Consilium Medicum). 2017; 3: 26–33.
________________________________________________
Zakharova I.N., Lavrova T.E., Talyzina M.F., Machneva E.B. A new look at prebiotics: hypotheses, trends, evidence. Pediatrics (Suppl. Consilium Medicum). 2017; 3: 26–33.
Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Аннотация
Уже более 20 лет по всему миру ведутся исследования, направленные на изучение структуры и функции пребиотиков – олигосахаридов. Селективное стимулирование роста полезных микроорганизмов кишечника позиционируется как главный критерий, определяющий эффект добавления в детские смеси пребиотиков. Однако уже давно известно, что эффекты пребиотиков выходят далеко за рамки влияния на кишечную микробиоту. Результаты клинических исследований доказывают влияние пребиотиков на иммунитет и снижение риска развития аллергии, а гипотеза о связи головного мозга и кишечника получает все больше доказательств в клинических исследованиях. В рамках этой концепции роль пребиотиков как «психобиотиков» становится еще более значимой. Появившиеся совсем недавно синтетические аналоги олигосахаридов грудного молока представляют собой новое направление в изучении пребиотиков. Также получены интересные данные по механизмам иммуномодулирующего действия олигосахаридов грудного молока. Очевидно, что полностью повторить состав олигосахаридов грудного молока невозможно.
Приблизиться к их свойствам и эффектам – достаточно амбициозная задача для производителей детских смесей. Таким образом, исследования пребиотиков продолжают быть одним их самых перспективных направлений в области изучения не только кишечной микробиоты, но и иммунитета, аллергии и психического здоровья.
Ключевые слова: пребиотики, олигосахариды, грудное молоко, искусственное вскармливание, психобиотики.
Приблизиться к их свойствам и эффектам – достаточно амбициозная задача для производителей детских смесей. Таким образом, исследования пребиотиков продолжают быть одним их самых перспективных направлений в области изучения не только кишечной микробиоты, но и иммунитета, аллергии и психического здоровья.
Ключевые слова: пребиотики, олигосахариды, грудное молоко, искусственное вскармливание, психобиотики.
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For more than 20 years, studies of prebiotic oligosaccharides have been conducted worldwide. Selective stimulation of useful intestinal microbiota is positioned as the main criterion in determining prebiotics. Nevertheless, it has long been known that the effects of prebiotics go well beyond the impact on the landscape of intestinal microbiota. The results of clinical studies prove the influence of prebiotics on immunity and development of allergies. The hypothesis about the connection between the brain and the gut gets more and more evidence in clinical studies. Within the framework of this concept, the role of prebiotics as "psychobiotics" becomes even more significant. Recently appeared synthetic analogs of human milk oligosaccharides (HMOs) represent a new direction in the study of prebiotics. Interesting data on the mechanisms of immunomodulation of human milk oligosaccharides have also been obtained. Obviously, it is impossible to completely replicate the composition of HMOs. Just approaching to their properties and effects is considered to be a quite ambitious task for manufacturers of infant formulas. Thus, studies of prebiotics continue to be one of the most promising scope in investiagations of not only the intestinal microbiota, but immunity, allergy and mental health as well.
Key words: prebiotics, oligosaccharides, breast milk, artificial feeding, psychobiotics.
Полный текст
Список литературы
1. Theis KR, Dheilly NM, Klassen JL et al. Getting the Hologenome Concept Right: an
Eco-Evolutionary Framework for Hosts and Their Microbiomes. M Systems 2016; 1 (2): e00028-16.
2. Catania F, Krohs U, ChittШ M et al. The hologenome consept: we need to incorporate function. Theory Biosci 2016; 12: 19.
3. Slattery J, MacFabe DF, Frye RE. The Significance of the Enteric Microbiome on the Development of Childhood Disease: A Review of Prebiotic and Probiotic Therapies in Disorders of Childhood. Clin Med Insights Pediatr 2016; 10: 91–107. eCollection 2016.
4. Bruzzese E, Volpicelli M, Squeglia V et al. A formula containing galacto- and fructo-
oligosaccahrides prevents intestinal and extra intestinal infections: An observational study. Clin Nutr 2009; 28: 156–61.
5. Arslanoglu S, Moro G, Schmitt J, Boehm G. Early Dietary Intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergy associated symptoms and infections during the first 2 years of life. J Nutr 2008; 138: 1091–5.
6. Moro G, Arslanoglu S, Stahl B et al. A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age. Arch Dis Child 2006; 91: 814–9.
7. Scholtens PA, Alliet P, Raes M et al. Fecal Secretory Immunoglobulin A Is Increased in Healthy Infants Who Receive a Formula with Short-Chain Galacto-Oligosaccharides and Long-Chain Fructo-Oligosaccharides. J Nutr 2008; 138: 1141–7.
8. Moro G, Minoli I, Mosca M et al. Dosage-Related Bifidogenic Effects of Galacto- and
Fructooligosaccharides in Formula-Fed Term Infants. J Pediatr Gastroenterol Nutr 2002; 34 (3): 291–5.
9. Grüber C et al. Immunoactive prebiotics transiently prevent occurrence of early
atopic dermatitis among low-atopy-risk infants. J Allergy Clin Immunol 2015; 136 (6): 1696–8.
10. Boyle RJ, Tang ML, Chiang WC et al. Prebiotic-supplemented partially hydrolysed cow’s milk formula for the prevention of eczema in high-risk infants: a randomized controlled trial. Allergy 2016; 71 (5): 701–10.
11. Arslanoglu S et al. Early neutral prebiotic oligosaccharide supplementation reduces the incidence of some allergic manifestations in the rst 5 years of life. J Biol Regul Homeost Agents 2012; 26 (Suppl. 3): 49–59.
12. Indrio F et al. Prebiotics improve gastric motiliy and gastric electricial activity in preterm newborns. JPGN 2009; 49 (2): 258–61.
13. Boehm G et al. Supplementation of bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants. Arch Dis Child 2002; 86 (3): F178–81.
14. Mihatsch W et al. Prebiotic oligosaccharides reduce stool viscosity and accelerate
gastrointestinal transport in preterm infants. Acta Paediatr 2006; 95 (7): 843–8.
15. Modi N et al. A randomized, double-blind, controlled trial of the effect of prebiotic
oligosaccharides on enteral tolerance in preterm infants. Pediatric Research 2010; 68: 440–5.
16. Dinan TG, Stanton C, Cryan JF. Review: Psychobiotics: a Novel Class of Psychotropic. Biol psychiatry 2013.
17. Sarkar A, Lehto SM, Harty S et al. Psychobiotics and the Manipulation of Bacteria- Gut-Brain Signals. Trends Neurosci 2016; 39 (11): 763–81.
18. Savignac HM et al. Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-d-aspartate receptor subunits and d-serine. Neurochem Int 2013;: 756–76.
19. Williams S et al. Neonatal prebiotic (BGOS) supplementation increases the levels of
synaptophysin, GluN2A-subunits and BDNF proteins in the adult rat hippocampus. Synapse 2016; 70 (3): 121–4.
20. Vázquez E et al. Effects of a human milk oligosaccharide, 2'-fucosyllactose, on hippocampal long-term potentiation and learning capabilities in rodents. J Nutr Biochem 2015; 26 (5): 455–65.
21. Burokas A, Arboleya S, Moloney RD et al. Targeting the Microbiota-Gut-Brain Axis: Prebiotics have anxiolytic and andepressant-like effects and reverse the impact of chronic stress in mice. Biol Psychiatry 2017; 82 (7): 472–87.
22. Schmidt K et al. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology (Berl) 2015; 232 (10): 1793–801.
23. Donovan SM, Comstock SS. Human Milk Oligosaccharides Influence Neonatal Mucosal and Systemic Immunity. Ann Nutr Metab 2016; 69 (Suppl. 2): 42–51.
24. Kulinich А, Li Liu. Human milk oligosaccharides: The role in the fine-tuning of innate immune responses. Carbohydr Res 2016; 432: 62–70.
25. Autran CA, Schoterman MH, Jantscher-Krenn E et al. Sialylated galacto-oligosac- charides and 2 -fucosyllactose reduce necrotizing enterocolitis in neonatal rats. Brit J Nutr 2016; 116: 294–9.
26. Seppo AE, Autran CA, Bode L, JКrvinen KM. Human milk oligosaccharides and de-
velopment of cow's milk allergy in infants. J Allergy Clin Immunol 2017; 139 (2): 708–11.
27. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on the essential composition of infant and follow-on formulae. EFSA J 2014; 12 (7): 3760.
28. Salminen S. Regulatory Aspects of Human Milk Oligosaccharides. Nestle Nutr Inst Workshop Ser 2017; 88: 161–70.
29. EFSA Panel on Dietetic Products, Nutrition and Allergies: Scientific opinion on the safety of 2’-0- fucosyllactose as a novel food ingredient pursuant to regulation (EC) No 258/97, 2015.
30. Puccio G et al. Effects of Infant Formula with human milk oligosaccharides on growth and morbidity: a randomized multicenter trial. JPGN 2017; 64 (4).
31. Marriage BJ, Buck RH, Goehring KC et al. Infants Fed a Lower Calorie Formula With 2'FL Show
Growth and 2'FL Uptake Like Breast-Fed Infants. J Pediatr Gastroenterol Nutr 2015; 61: 649–58.
32. Goehring KC, Marriage BJ, Oliver JS et al. Similar to Those Who Are Breastfed, Infants Fed a Formula Containing 2'-Fucosyllactose Have Lower Inflammatory Cytokines in a Randomized Controlled Trial. J Nutr 2016; 146 (12): 2559–66.
Eco-Evolutionary Framework for Hosts and Their Microbiomes. M Systems 2016; 1 (2): e00028-16.
2. Catania F, Krohs U, ChittШ M et al. The hologenome consept: we need to incorporate function. Theory Biosci 2016; 12: 19.
3. Slattery J, MacFabe DF, Frye RE. The Significance of the Enteric Microbiome on the Development of Childhood Disease: A Review of Prebiotic and Probiotic Therapies in Disorders of Childhood. Clin Med Insights Pediatr 2016; 10: 91–107. eCollection 2016.
4. Bruzzese E, Volpicelli M, Squeglia V et al. A formula containing galacto- and fructo-
oligosaccahrides prevents intestinal and extra intestinal infections: An observational study. Clin Nutr 2009; 28: 156–61.
5. Arslanoglu S, Moro G, Schmitt J, Boehm G. Early Dietary Intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergy associated symptoms and infections during the first 2 years of life. J Nutr 2008; 138: 1091–5.
6. Moro G, Arslanoglu S, Stahl B et al. A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age. Arch Dis Child 2006; 91: 814–9.
7. Scholtens PA, Alliet P, Raes M et al. Fecal Secretory Immunoglobulin A Is Increased in Healthy Infants Who Receive a Formula with Short-Chain Galacto-Oligosaccharides and Long-Chain Fructo-Oligosaccharides. J Nutr 2008; 138: 1141–7.
8. Moro G, Minoli I, Mosca M et al. Dosage-Related Bifidogenic Effects of Galacto- and
Fructooligosaccharides in Formula-Fed Term Infants. J Pediatr Gastroenterol Nutr 2002; 34 (3): 291–5.
9. Grüber C et al. Immunoactive prebiotics transiently prevent occurrence of early
atopic dermatitis among low-atopy-risk infants. J Allergy Clin Immunol 2015; 136 (6): 1696–8.
10. Boyle RJ, Tang ML, Chiang WC et al. Prebiotic-supplemented partially hydrolysed cow’s milk formula for the prevention of eczema in high-risk infants: a randomized controlled trial. Allergy 2016; 71 (5): 701–10.
11. Arslanoglu S et al. Early neutral prebiotic oligosaccharide supplementation reduces the incidence of some allergic manifestations in the rst 5 years of life. J Biol Regul Homeost Agents 2012; 26 (Suppl. 3): 49–59.
12. Indrio F et al. Prebiotics improve gastric motiliy and gastric electricial activity in preterm newborns. JPGN 2009; 49 (2): 258–61.
13. Boehm G et al. Supplementation of bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants. Arch Dis Child 2002; 86 (3): F178–81.
14. Mihatsch W et al. Prebiotic oligosaccharides reduce stool viscosity and accelerate
gastrointestinal transport in preterm infants. Acta Paediatr 2006; 95 (7): 843–8.
15. Modi N et al. A randomized, double-blind, controlled trial of the effect of prebiotic
oligosaccharides on enteral tolerance in preterm infants. Pediatric Research 2010; 68: 440–5.
16. Dinan TG, Stanton C, Cryan JF. Review: Psychobiotics: a Novel Class of Psychotropic. Biol psychiatry 2013.
17. Sarkar A, Lehto SM, Harty S et al. Psychobiotics and the Manipulation of Bacteria- Gut-Brain Signals. Trends Neurosci 2016; 39 (11): 763–81.
18. Savignac HM et al. Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-d-aspartate receptor subunits and d-serine. Neurochem Int 2013;: 756–76.
19. Williams S et al. Neonatal prebiotic (BGOS) supplementation increases the levels of
synaptophysin, GluN2A-subunits and BDNF proteins in the adult rat hippocampus. Synapse 2016; 70 (3): 121–4.
20. Vázquez E et al. Effects of a human milk oligosaccharide, 2'-fucosyllactose, on hippocampal long-term potentiation and learning capabilities in rodents. J Nutr Biochem 2015; 26 (5): 455–65.
21. Burokas A, Arboleya S, Moloney RD et al. Targeting the Microbiota-Gut-Brain Axis: Prebiotics have anxiolytic and andepressant-like effects and reverse the impact of chronic stress in mice. Biol Psychiatry 2017; 82 (7): 472–87.
22. Schmidt K et al. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology (Berl) 2015; 232 (10): 1793–801.
23. Donovan SM, Comstock SS. Human Milk Oligosaccharides Influence Neonatal Mucosal and Systemic Immunity. Ann Nutr Metab 2016; 69 (Suppl. 2): 42–51.
24. Kulinich А, Li Liu. Human milk oligosaccharides: The role in the fine-tuning of innate immune responses. Carbohydr Res 2016; 432: 62–70.
25. Autran CA, Schoterman MH, Jantscher-Krenn E et al. Sialylated galacto-oligosac- charides and 2 -fucosyllactose reduce necrotizing enterocolitis in neonatal rats. Brit J Nutr 2016; 116: 294–9.
26. Seppo AE, Autran CA, Bode L, JКrvinen KM. Human milk oligosaccharides and de-
velopment of cow's milk allergy in infants. J Allergy Clin Immunol 2017; 139 (2): 708–11.
27. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on the essential composition of infant and follow-on formulae. EFSA J 2014; 12 (7): 3760.
28. Salminen S. Regulatory Aspects of Human Milk Oligosaccharides. Nestle Nutr Inst Workshop Ser 2017; 88: 161–70.
29. EFSA Panel on Dietetic Products, Nutrition and Allergies: Scientific opinion on the safety of 2’-0- fucosyllactose as a novel food ingredient pursuant to regulation (EC) No 258/97, 2015.
30. Puccio G et al. Effects of Infant Formula with human milk oligosaccharides on growth and morbidity: a randomized multicenter trial. JPGN 2017; 64 (4).
31. Marriage BJ, Buck RH, Goehring KC et al. Infants Fed a Lower Calorie Formula With 2'FL Show
Growth and 2'FL Uptake Like Breast-Fed Infants. J Pediatr Gastroenterol Nutr 2015; 61: 649–58.
32. Goehring KC, Marriage BJ, Oliver JS et al. Similar to Those Who Are Breastfed, Infants Fed a Formula Containing 2'-Fucosyllactose Have Lower Inflammatory Cytokines in a Randomized Controlled Trial. J Nutr 2016; 146 (12): 2559–66.
________________________________________________
1. Theis KR, Dheilly NM, Klassen JL et al. Getting the Hologenome Concept Right: an
Eco-Evolutionary Framework for Hosts and Their Microbiomes. M Systems 2016; 1 (2): e00028-16.
2. Catania F, Krohs U, ChittШ M et al. The hologenome consept: we need to incorporate function. Theory Biosci 2016; 12: 19.
3. Slattery J, MacFabe DF, Frye RE. The Significance of the Enteric Microbiome on the Development of Childhood Disease: A Review of Prebiotic and Probiotic Therapies in Disorders of Childhood. Clin Med Insights Pediatr 2016; 10: 91–107. eCollection 2016.
4. Bruzzese E, Volpicelli M, Squeglia V et al. A formula containing galacto- and fructo-
oligosaccahrides prevents intestinal and extra intestinal infections: An observational study. Clin Nutr 2009; 28: 156–61.
5. Arslanoglu S, Moro G, Schmitt J, Boehm G. Early Dietary Intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergy associated symptoms and infections during the first 2 years of life. J Nutr 2008; 138: 1091–5.
6. Moro G, Arslanoglu S, Stahl B et al. A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age. Arch Dis Child 2006; 91: 814–9.
7. Scholtens PA, Alliet P, Raes M et al. Fecal Secretory Immunoglobulin A Is Increased in Healthy Infants Who Receive a Formula with Short-Chain Galacto-Oligosaccharides and Long-Chain Fructo-Oligosaccharides. J Nutr 2008; 138: 1141–7.
8. Moro G, Minoli I, Mosca M et al. Dosage-Related Bifidogenic Effects of Galacto- and
Fructooligosaccharides in Formula-Fed Term Infants. J Pediatr Gastroenterol Nutr 2002; 34 (3): 291–5.
9. Grüber C et al. Immunoactive prebiotics transiently prevent occurrence of early
atopic dermatitis among low-atopy-risk infants. J Allergy Clin Immunol 2015; 136 (6): 1696–8.
10. Boyle RJ, Tang ML, Chiang WC et al. Prebiotic-supplemented partially hydrolysed cow’s milk formula for the prevention of eczema in high-risk infants: a randomized controlled trial. Allergy 2016; 71 (5): 701–10.
11. Arslanoglu S et al. Early neutral prebiotic oligosaccharide supplementation reduces the incidence of some allergic manifestations in the rst 5 years of life. J Biol Regul Homeost Agents 2012; 26 (Suppl. 3): 49–59.
12. Indrio F et al. Prebiotics improve gastric motiliy and gastric electricial activity in preterm newborns. JPGN 2009; 49 (2): 258–61.
13. Boehm G et al. Supplementation of bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants. Arch Dis Child 2002; 86 (3): F178–81.
14. Mihatsch W et al. Prebiotic oligosaccharides reduce stool viscosity and accelerate
gastrointestinal transport in preterm infants. Acta Paediatr 2006; 95 (7): 843–8.
15. Modi N et al. A randomized, double-blind, controlled trial of the effect of prebiotic
oligosaccharides on enteral tolerance in preterm infants. Pediatric Research 2010; 68: 440–5.
16. Dinan TG, Stanton C, Cryan JF. Review: Psychobiotics: a Novel Class of Psychotropic. Biol psychiatry 2013.
17. Sarkar A, Lehto SM, Harty S et al. Psychobiotics and the Manipulation of Bacteria- Gut-Brain Signals. Trends Neurosci 2016; 39 (11): 763–81.
18. Savignac HM et al. Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-d-aspartate receptor subunits and d-serine. Neurochem Int 2013;: 756–76.
19. Williams S et al. Neonatal prebiotic (BGOS) supplementation increases the levels of
synaptophysin, GluN2A-subunits and BDNF proteins in the adult rat hippocampus. Synapse 2016; 70 (3): 121–4.
20. Vázquez E et al. Effects of a human milk oligosaccharide, 2'-fucosyllactose, on hippocampal long-term potentiation and learning capabilities in rodents. J Nutr Biochem 2015; 26 (5): 455–65.
21. Burokas A, Arboleya S, Moloney RD et al. Targeting the Microbiota-Gut-Brain Axis: Prebiotics have anxiolytic and andepressant-like effects and reverse the impact of chronic stress in mice. Biol Psychiatry 2017; 82 (7): 472–87.
22. Schmidt K et al. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology (Berl) 2015; 232 (10): 1793–801.
23. Donovan SM, Comstock SS. Human Milk Oligosaccharides Influence Neonatal Mucosal and Systemic Immunity. Ann Nutr Metab 2016; 69 (Suppl. 2): 42–51.
24. Kulinich А, Li Liu. Human milk oligosaccharides: The role in the fine-tuning of innate immune responses. Carbohydr Res 2016; 432: 62–70.
25. Autran CA, Schoterman MH, Jantscher-Krenn E et al. Sialylated galacto-oligosac- charides and 2 -fucosyllactose reduce necrotizing enterocolitis in neonatal rats. Brit J Nutr 2016; 116: 294–9.
26. Seppo AE, Autran CA, Bode L, JКrvinen KM. Human milk oligosaccharides and de-
velopment of cow's milk allergy in infants. J Allergy Clin Immunol 2017; 139 (2): 708–11.
27. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on the essential composition of infant and follow-on formulae. EFSA J 2014; 12 (7): 3760.
28. Salminen S. Regulatory Aspects of Human Milk Oligosaccharides. Nestle Nutr Inst Workshop Ser 2017; 88: 161–70.
29. EFSA Panel on Dietetic Products, Nutrition and Allergies: Scientific opinion on the safety of 2’-0- fucosyllactose as a novel food ingredient pursuant to regulation (EC) No 258/97, 2015.
30. Puccio G et al. Effects of Infant Formula with human milk oligosaccharides on growth and morbidity: a randomized multicenter trial. JPGN 2017; 64 (4).
31. Marriage BJ, Buck RH, Goehring KC et al. Infants Fed a Lower Calorie Formula With 2'FL Show
Growth and 2'FL Uptake Like Breast-Fed Infants. J Pediatr Gastroenterol Nutr 2015; 61: 649–58.
32. Goehring KC, Marriage BJ, Oliver JS et al. Similar to Those Who Are Breastfed, Infants Fed a Formula Containing 2'-Fucosyllactose Have Lower Inflammatory Cytokines in a Randomized Controlled Trial. J Nutr 2016; 146 (12): 2559–66.
Авторы
И.Н.Захарова1, Т.Е.Лаврова*2, М.Ф.Талызина2, Е.Б.Мачнева1
1 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России. 125993, Россия, Москва, ул. Баррикадная, д. 2/1;
2 ООО «Нутриция». 143421, Россия, Московская область, Красногорский р-н, 26-й км автодороги «Балтия», бизнес-центр «Рига Ленд», стр. 1
*Tatyana.LAVROVA@danone.com
1 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России. 125993, Россия, Москва, ул. Баррикадная, д. 2/1;
2 ООО «Нутриция». 143421, Россия, Московская область, Красногорский р-н, 26-й км автодороги «Балтия», бизнес-центр «Рига Ленд», стр. 1
*Tatyana.LAVROVA@danone.com
________________________________________________
I.N.Zakharova1, T.E.Lavrova*2, M.F.Talyzina2, E.B.Machneva1
1 Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation. 125993, Russian Federation, Moscow, st. Barrikadnaia, 2/1;
2 "Nutricia". 143421, Russian Federation, Moscow region, Krasnogorskii area, Baltia highway, 26th km, business-centre "Riga Lend", building 1
*Tatyana.LAVROVA@danone.com
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