Кишечная микробиота и аллергия. Про- и пребиотики в профилактике и лечении аллергических заболеваний

Микробиота кишечника является фактором, в значительной степени определяющим здоровье человека. Воздействие на ребенка микробного фактора начинается задолго до рождения, и определенные особенности формирования иммунного ответа и микробиоценоза кишечника дети имеют еще до рождения. Для детей с аллергическими заболеваниями характерно снижение разнообразия кишечной микробиоты в первые месяцы жизни — еще до развития аллергической патологии. Возможности корректировать процесс формирования микробиоты достаточно ограничены, однако показано, что раннее (в течение первых часов жизни) прикладывание к груди, грудное вскармливание в течение как минимум первых 6 мес жизни, использование пребиотиков в составе детских молочных смесей, а также применение пробиотиков с доказанной эффективностью может давать положительные эффекты в отношении профилактики аллергии. В обзоре приведены основные выводы последних метаанализов и согласительных документов международных медицинских сообществ в отношении возможности использования про- и пребиотиков в профилактике и лечении аллергических заболеваний. Несмотря на большой научный и практический интерес к проблеме, авторы метаанализов указывают на недостаточное количество клинических исследований, проведенных с соблюдением принципов доказательной медицины.

1. Turnbaugh PJ, Ley RE, Hamady M, et al. The human microbiome project. Nature. 2007;449(7164):804–810. doi: 10.1038/nature06244.

2. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207–214. doi: 10.1038/nature11234.

3. Human Microbiome Project Consortium. A framework for human microbiome research. Nature. 2012;486(7402):215–221. doi: 10.1038/nature11209.

4. Belda-Ferre P, Alcaraz LD, Cabrera-Rubio R, et al. The oral metagenome in health and disease. ISME J. 2012;6(1):46–56. doi: 10.1038/ismej.2011.85.

5. Goodacre R. Metabolomics of a superorganism. J Nutr. 2007;137(1 Suppl):259S–266S. doi: 10.1093/jn/137.1.259S.

6. Kho ZY, Lal SK. The human gut microbiome — a potential controller of wellness and disease. frontiers in microbiology. Front Microbiol. 2018;9:1835. doi: 10.3389/fmicb.2018.01835.

7. Kau AL, Ahern PP, Griffin NW, et al. Human nutrition, the gut microbiome and the immune system. Nature. 2011;474(7351):327– 336. doi: 10.1038/nature10213.

8. Payne MS, Bayatibojakhi S. Exploring preterm birth as a polymicrobial disease: an overview of the uterine microbiome. Front Immunol. 2014;5:595. doi: 10.3389/fimmu.2014.00595.

9. Claesson MJ, Jeffery IB, Conde S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488(7410):178–184. doi: 10.1038/nature11319.

10. Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–180. doi: 10.1038/nature09944.

11. Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105–108. doi: 10.1126/science.1208344.

12. Jeffery IB, Claesson MJ, O’Toole PW, Shanahan F. Categorization of the gut microbiota: enterotypes or gradients? Nature Rev Microbiol. 2012;10(9):591–592. doi: 10.1038/nrmicro2859.

13. Урсова Н.И. Основные физиологические функции интестинальной микрофлоры и формирование микробиоценоза у детей // Вопросы практической педиатрии. — 2006. — Т. 1. — №1. — С. 51–57.

14. Feng T, Elson CO. Adaptive immunity in the host-microbiota dialog. Mucosal Immunol. 2011;4(1):15–21. doi: 10.1038/mi.2010.60.

15. Шендеров Б.А. Медицинская микробная экология и функциональное питание. Т.1: Микрофлора человека и животных и ее функции. — М.: ГРАНТЪ; 1998. — 288 с.

16. Bäckhed F. Programming of host metabolism by the gut microbiota. Ann Nutr Metab. 2011;58 Suppl 2:44–52. doi: 10.1159/000328042.

17. Clarke G, Stilling RM, Kennedy PJ, et al. Minireview: gut microbiota: the neglected endocrine organ. Mol Endocrinol. 2014;28(8):1221–1238. doi: 10.1210/me.2014-1108.

18. Bäckhed F, Ding H, Wang T, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004;101(44):15718–15723. doi: 10.1073/pnas.0407076101.

19. Vijay-Kumar M, Aitken JD, Carvalho FA, et al. Metabolic syndrome and altered gut microbiota in mice lacking toll-like receptor 5. Science. 2010;328(5975):228–231. doi: 10.1126/science.1179721.

20. Fleissner CK, Huebel N, Abd El-Bary MM, et al. Absence of intestinal microbiota does not protect mice from diet-induced obesity. Br J Nutr. 2010;104(6):919–929. doi: 10.1017/S0007114510001303.

21. Lyte M. The microbial organ in the gut as a driver of homeostasis and disease. Med Hypotheses. 2010;74(4):634–638. doi: 10.1016/j.mehy.2009.10.025.

22. Tanaka M, Nakayama J. Development of the gut microbiota in infancy and its impact on health in later life. Allergol Int. 2017;66(4):515–522. doi: 10.1016/j.alit.2017.07.010.

23. Wesemann DR, Nagler CR. The microbiome, timing, and barrier function in the context of allergic disease. Immunity. 2016;44(4):728–738. doi: 10.1016/j.immuni.2016.02.002.

24. Koenig JE, Spor A, Scalfone N, et al. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A. 2011;108 Suppl 1:4578–4585. doi: 10.1073/pnas.1000081107.

25. Romano-Keeler J, Weitkamp J-H. Maternal influences on fetal microbial colonization and immune development. Pediatr Res. 2015;77(0):189–195. doi: 10.1038/pr.2014.163.

26. DiGiulio DB. Diversity of microbes in amniotic fluid. Semin Fetal Neonatal Med. 2012;17(1):2–11. doi: 10.1016/j.siny.2011.10.001.

27. Mendz GL, Kaakoush NO, Quinlivan JA. Bacterial aetiological agents of intraamniotic infections and preterm birth in pregnant women. Front Cell Infect Microbiol. 2013;3:58. doi: 10.3389/fcimb.2013.00058.

28. Perez PF, Doré J, Leclerc M, et al. Bacterial imprinting of the neonatal immune system: lessons from maternal cells? Pediatrics. 2007;119(3):e724–732. doi: 10.1542/peds.2006-1649.

29. Rescigno M, Rotta G, Valzasina B, Ricciardi-Castagnoli P. Dendritic cells shuttle microbes across gut epithelial monolayers. Immunobiology. 2001;204(5):572–581. doi: 10.1078/0171-2985-00094.

30. Lelouard H, Fallet M, de Bovis B, et al. Peyer’s patch dendritic cells sample antigens by extending dendrites through M cell-specific transcellular pores. Gastroenterology. 2012;142(3):592–601.e3. doi: 10.1053/j.gastro.2011.11.039.

31. McDole JR, Wheeler LW, McDonald KG, et al. Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature. 2012;483(7389):345–349. doi: 10.1038/nature10863.

32. Round JL, Mazmanian SK. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci U S A. 2010;107(27):12204–12209. doi: 10.1073/pnas.0909122107.

33. Dingle BM, Liu Y, Fatheree NY, et al. FoxP3+ regulatory T cells attenuate experimental necrotizing enterocolitis. PLoS One. 2013;8(12):e82963. doi: 10.1371/journal.pone.0082963.

34. Stappenbeck TS, Hooper LV, Gordon JI. Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci U S A. 2002;99(24):15451–15455. doi: 10.1073/pnas.202604299.

35. Weng M, Walker WA. The role of gut microbiota in programming the immune phenotype. J Dev Orig Health Dis. 2013;4(3):203–214. doi: 10.1017/S2040174412000712.

36. Макарова С.Г., Болдырева М.Н., Лаврова Т.Е., Петровская М.И. Кишечный микробиоценоз, пищевая толерантность и пищевая аллергия. Современное состояние проблемы // Вопросы современной педиатрии. — 2014. — Т.13. — №3. — С. 21–29. doi: 10.15690/vsp.v13i3.1024.

37. Huurre A, Kalliomaki M, Rautava S, et al. Mode of delivery — effects on gut microbiota and humoral immunity. Neonatology. 2008;93(4):236–240. doi: 10.1159/000111102.

38. Azad MB, Konya T, Maughan H, et al. Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ. 2013;185(5):385–394. doi: 10.1503/cmaj.121189.

39. Dominguez-Bello MG, Costello EK, Contreras M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A. 2010;107(26):11971–11985. doi: 10.1073/pnas.1002601107.

40. Laubereau B, Filipiak-Pittroff B, von Berg A, et al. Caesarean section and gastrointestinal symptoms, atopic dermatitis and sensiti zation during the first year of life. Arch Dis Child. 2004;89:993–997. doi: 10.1136/adc.2003.043265.

41. Renz-Polster H, David MR, Buist AS, et al. Caesarean section delivery and the risk of allergic disorders in childhood. Clin Exp Allergy. 2005;35(11):1466–1472. doi: 10.1111/j.1365-2222.2005.02356.x.

42. Thavagnanam S., Fleming J., Bromley A., et al. A meta-analysis of the association between Caesarean section and childhood asthma. Clin Exp Allergy. 2008;38(4):629–633. doi: 10.1111/j.1365-2222.2007.02780.x.

43. Kristensen K, Henriksen L. Cesarean section and disease associated with immune function. J Allergy Clin Immunol. 2016;137(2):587–590. doi: 10.1016/j.jaci.2015.07.040.

44. Tanaka S, Kobayashi T, Songjinda P, et al. Influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota. FEMS Immunol Med Microbiol. 2009;56(1):80– 87. doi: 10.1111/j.1574-695X.2009.00553.x.

45. Fouhy F, Guinane CM, Hussey S, et al. High-throughput sequencing reveals the incomplete, short-term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin. Antimicrob Agents Chemother. 2012;56(11):5811– 5820. doi: 10.1128/AAC.00789-12.

46. Greenwood C, Morrow AL, Lagomarcino AJ, et al. Early empiric antibiotic use in preterm infants is associated with lower bacterial diversity and higher relative abundance of Enterobacter. J Pediatr. 2014;165(1):23–29. doi: 10.1016/j.jpeds.2014.01.010.

47. Moore AM, Ahmadi S, Patel S, et al. Gut resistome development in healthy twin pairs in the first year of life. Microbiome. 2015;3:27. doi: 10.1186/s40168-015-0090-9.

48. Hall MA, Cole CB, Smith SL, et al. Factors influencing the presence of faecal lactobacilli in early infancy. Arch Dis Child. 1990;65(2):185–188. doi: 10.1136/adc.65.2.185.

49. Jernberg C, Lofmark S, Edlund C. Long term ecological impacts of antibiotic administration on the human intestinal microbiota. ISME J. 2007;1(1):56–66. doi: 10.1038/ismej.2007.3.

50. Hanson LA, Korotkova M, Telemo E. Breast-feeding, infant formulas, and the immune system. Ann Allergy Asthma Immunol. 2003;90(6 Suppl 3):59–63.

51. Andreas NJ, Kampmann B, Mehring Le-Doare K. Human breast milk: a review on its composition and bioactivity. Early Hum Dev. 2015;91(11):629–635. doi: 10.1016/j.earlhumdev.2015.08.013.

52. Martin R, Langa S, Reviriego C, et al. Human milk is a source of lactic acid bacteria for the infant gut. doi: 10.1016/j.jpeds.2003.09.028.

53. Jeurink PV, van Bergenhenegouwen J, Jiménez E, et al. Human milk: a source of more life than we imagine. Benef Microbes. 2013;4(1):17–30. doi: 10.3920/BM2012.0040.

54. Murgas Torrazza R, Neu J. The developing intestinal microbiome and its relationship to health and disease in the neonate. J Perinatol. 2011;31 Suppl 1:S29–34. doi: 10.1038/jp.2010.172.

55. Heinig MJ. Host defense benefits of breastfeeding for the infant. Effect of breastfeeding duration and exclusivity. Pediatr Clin North Am. 2001;48(1):105–23, ix. doi: 10.1016/s0031-3955(05)70288-1.

56. Sharon M, Wang DM, Li M, et al. Host microbe interactions in the neonatal intestine: role of human milk oligosaccharides. Adv Nutr. 2012;3(3):450–455. doi: 10.3945/an.112.001859.

57. Azad MB, Robertson B, Atakora F, et al. Human milk oligosaccharide concentrations are associated with multiple fixed and modifiable maternal characteristics, environmental factors, and feeding practices. J Nutr. 2018;148(11):1733–1742. doi: 10.1093/jn/nxy175.

58. Turroni F, Milani C, van Sinderen D, Ventura M. Genetic strategies for mucin metabolism in Bifidobacterium bifidum PRL2010: an example of possible human-microbe co-evolution. Gut Microbes. 2011;2(3):183–189. doi: 10.4161/gmic.2.3.16105.

59. Sela DA, Chapman J, Adeuya A, et al. The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome. Proc Natl Acad Sci U S A. 2008;105(48):18964–18969. doi: 10.1073/pnas.0809584105.

60. Ayechu-Muruzabal V, van Stigt AH, Mank M, et al. Diversity of human milk oligosaccharides and effects on early life immune development. Front Pediatr. 2018;6:239. doi: 10.3389/fped.2018.00239.

61. Donovan SM, Comstock SS. Human milk oligosaccharides influence neonatal mucosal and systemic immunity. Ann Nutr Metab. 2016;69 Suppl 2:42–51. doi: 10.1159/000452818.

62. Frei R, Lauener RP, Crameri R, O’Mahony L. Microbiota and dietary interactions — an update to the hygiene hypothesis? Allergy. 2012;67(4):S451–461. doi: 10.1111/j.1398-9995.2011.02783.x.

63. Russel FD, Burgin-Maunder CS. Distinguishing health benefits of eicosapentaenoic and docosahexaenoic acids. Mar Drugs. 2012;10(11):2535–2559. doi: 10.3390/md10112535.

64. Miliku K, Robertson B, Sharma AK, et al. Human milk oligosaccharide profiles and food sensitization among infants in the CHILD Study. Allergy. 2018;73(10):2070–2073. doi: 10.1111/all.13476.

65. Doherty AM, Lodge CJ, Dharmage SC, et al. Human milk oligosaccharides and associations with immune-mediated disease and infection in childhood: a systematic review. Front Pediatr. 2018;6:91. doi: 10.3389/fped.2018.00091.

66. Prescott SL, Noakes P, Chow BW, et al. Presymptomatic differences in Toll-like receptor function in infants who have allergy. J Allergy Clin Immunol. 2008;122(2):391–399, 399.e1–5. doi: 10.1016/j.jaci.2008.04.042.

67. Wang M, Karlsson C, Olsson C, et al. Reduced diversity in the early fecal microbiota of infants with atopic eczema. J Allergy Clin Immunol. 2008;121(1):129–134. doi: 10.1016/j.jaci.2007.09.011.

68. Peterson DA, McNulty NP, Guruge JL, Gordon JI. IgA response to symbiotic bacteria as a mediator of gut homeostasis. Cell Host Microbe. 2007;2(5):328–339. doi: 10.1016/j.chom.2007.09.013.

69. Noval Rivas M, Burton OT, Wise P, et al. Regulatory T-cell reprogramming toward a Th2-cell-like lineage impairs oral tolerance and promotes food allergy. Immunity. 2015;42(3):512–523. doi: 10.1016/j.immuni.2015.02.004.

70. Lee JB, Chen CY, Liu B, et al. IL-25 and CD4(+) TH2 cells enhance type 2 innate lymphoid cell-derived IL-13 production,which promotes IgE-mediated experimental food allergy. J Allergy Clin Immunol. 2016;137(4):1216–1225.e5. doi: 10.1016/j.jaci.2015.09.019.

71. Cahenzli J, Köller Y, Wyss M, et al. Intestinal microbial diversity during early-life colonization shapes long-term IgE levels. Cell Host Microbe. 2013;14(5):559–570. doi: 10.1016/j.chom.2013.10.004.

72. Hill DA, Siracusa MC, Abt MC, et al. Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med. 2012;18(4):538–546. doi: 10.1038/nm.2657.

73. Abrahamsson TR, Jakobsson HE, Andersson AF, et al. Low diversity of the gut microbiota in infants with atopic eczema. J Allergy Clin Immunol. 2012;129(2):434–440, 440.e1–2. doi: 10.1016/j.jaci.2011.10.025.

74. Azad MB, Konya T, Guttman DS, et al.; CHILD Study Investigators. Infant gut microbiota and food sensitization: associations in the first year of life. Clin Exp Allergy. 2015;45(3):632–643. doi: 10.1111/cea.12487.

75. Ismail IH, Oppedisano F, Joseph SJ, et al. Tang reduced gut microbial diversity in early life is associated with later development of eczema but not atopy in high-risk infants. Pediatr Allergy Immunol. 2012;23(7):674–681. doi: 10.1111/j.1399-3038.2012.01328.x.

76. Sjögren YM, Jenmalm MC, Böttcher MF, et al. Altered early infant gut microbiota in children developing allergy up to 5 years of age. Clin Exp Allergy. 2009;39(4):518–526. doi: 10.1111/j.1365-2222.2008.03156.x.

77. Nylund L, Satokari R, Nikkilä J, et al. Microarray analysis reveals marked intestinal microbiota aberrancy in infants having eczema compared to healthy children in at-risk for atopic disease. BMC Microbiol. 2013;13:12. doi: 10.1186/1471-2180-13-12.

78. Ling Z, Li Z, Liu X, et al. Altered fecal microbiota composition for food allergy in infants. Appl Environ Microbiol. 2014;80(8):2546– 2554. doi: 10.1128/AEM.00003-14.

79. McGuckin MA, Linden SK, Sutton P, Florin TH. Mucin dynamics and enteric pathogens. Nat Rev Microbiol. 2011;9(4):265–278. doi: 10.1038/nrmicro2538.

80. Jakobsson HE, Abrahamsson TR, Jenmalm MC, et al. Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section. Gut. 2014;63(4):559–566. doi: 10.1136/gutjnl-2012-303249.

81. Bunyavanich S, Shen N, Grishin A, et al. Early-life gut microbiome composition and milk allergy resolution. J Allergy Clin Immunol. 2016;138(4):1122–1130. doi: 10.1016/j.jaci.2016.03.041.

82. Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria: Report of a Joint FAO WHO Expert Consultation on evaluation of health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. Cordoba; 2001. 34 p. Available from: www.fao.org.

83. Collins JK, Thornton G, Sullivan GO. Selection of probiotic strains for human application. Int Dairy J. 1998;8(5–6):487–490. doi: 10.1016/s0958-6946(98)00073-9.

84. Ouwehand AC, Salminen S, Isolauri E. Probiotics: an overview of beneficial effects. Antonie Van Leeuwenhoek. 2002;82(1–4):279– 289. doi: 10.1023/a:1020620607611.

85. Gorbach SL. Probiotics in the third millennium. Digest Liver Dis. 2002;34(Suppl 2):S2–S7. doi: 10.1016/s1590-8658(02)80155-4.

86. McFarland. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol. 2006;101(4):812–822. doi: 10.1111/j.1572-0241.2006.00465.x.

87. Корниенко Е.А. Современные принципы выбора пробиотиков // Детские инфекции. — 2007. — Т.6. — №3. — С. 64–69.

88. Rijkers GT, Bengmark S, Enck P, et al. Guidance for substantiating the evidence for beneficial effects of probiotics: current status and recommendations for future research. J Nutr. 2010;140(3):671– 676. doi: 10.3945/jn.109.113779.

89. Hajavi J, Esmaeili SA, Varasteh AR, et al. The immunomodulatory role of probiotics in allergy therapy. J Cell Physiol. 2019;234(3):2386– 2398. doi: 10.1002/jcp.27263.

90. Fiocchi A, Pawankar R, Cuello-Garcia C, et al. World Allergy Organization – McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics. World Allergy Organ J. 2015;8(1):4. doi: 10.1186/s40413-015-0055-2.

91. Boyle RJ, Ismail IH, Kivivuori S, et al. Lactobacillus GG treatment during pregnancy for the prevention of eczema: a randomized controlled trial. Allergy. 2011;66(4):509–516. doi: 10.1111/j.1398-9995.2010.02507.x.

92. Dotterud CK, Storro O, Johnsen R, Oien T. Probiotics in pregnant women to prevent allergic disease: a randomized, double-blind trial. Br J Dermatol. 2010;163(3):616–623. doi: 10.1111/j.1365-2133.2010.09889.x.

93. Huurre A, Laitinen K, Rautava S, et al. Impact of maternal atopy and probiotic supplementation during pregnancy on infant sensitization: a double-blind placebo-controlled study. Clin Exp Allergy. 2008;38(8):1342–1348. doi: 10.1111/j.1365-2222.2008.03008.x.

94. Ortiz-Andrellucchi A, Sanchez-Villegas A, Rodriguez-Gallego C, et al. Immunomodulatory effects of the intake of fermented milk with Lactobacillus casei DN114001 in lactating mothers and their children. Br J Nutr. 2008;100(4):834–845. doi: 10.1017/S0007114508959183.

95. Food allergy and anaphylaxis guidelines. EAACI. 2014. 278 p. [updated 2016 Oct 1; cited 2017 May 26]. Available from: http://www.eaaci.org/resources/guidelines/faa-guidelines.html.

96. Martín-Muñoz MF, Fortuni M, Caminoa M, et al. Anaphylactic reaction to probiotics. Cow’s milk and hen’s egg allergens in probiotic compounds. Pediatr Allergy Immunol. 2012;23(8):778– 784. doi: 10.1111/j.1399-3038.2012.01338.x.

97. Sharma G, Im SH. Probiotics as a potential immunomodulating pharmabiotics in allergic diseases: current status and future prospects. Allergy Asthma Immunol Res. 2018;10(6):575–590. doi: 10.4168/aair.2018.10.6.575.

98. Prakoeswa CR, Herwanto N, Prameswari R, et al. Lactobacillus plantarum IS-10506 supplementation reduced SCORAD in children with atopic dermatitis. Benef Microbes. 2017;8(5):833–840. doi: 10.3920/BM2017.0011.

99. Zhang J, Ma JY, Li QH, et al. Lactobacillus rhamnosus GG induced protective effect on allergic airway inflammation is associated with gut microbiota. Cell Immunol. 2018;332:77–84. doi: 10.1016/j./cellimm.2018.08.002.

100. Das RR, Singh M, Shafiq N. Probiotics in treatment of allergic rhinitis. World Allergy Organ J. 2010;3(9):239–244. doi: 10.1097/WOX.0b013e3181f234d4.

101. Marcinkowska M, Zagorska A, Fajkis N, et al. Probiotic supplementation and topical application in the treatment of pediatric atopic dermatitis. Curr Pharm Biotechnol. 2018;19(10):827–838. doi: 10.2174/1389201019666181008113149.

102. Fassio F, Guagnini F. House dust mite-related respiratory allergies and probiotics: a narrative review. Clin Mol Allergy. 2018;16:15. doi: 10.1186/s12948-018-0092-9.

103. Cuello-Garcia CA, Fiocchi A, Pawankar R, et al. World Allergy Organization – McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics. World Allergy Organ J. 2016;9:10. doi: 10.1186/s40413-016-0102-7.

104. Agostoni C, Axelsson I, Goulet O, et al. Prebiotic oligosaccharides in dietetic products for infants: a commentary by the ESPGHAN Committee on Nutrition.J Pediatr Gastroenterol Nutr. 2004;39(5):465– 73. doi: 10.1097/00005176-200411000-00003.

105. Gibson GR, Probert HM, Loo JV, et al. Dietary modulation of the human colonic microbiota: updating the concept of prebiotics. Nutr Res Rev. 2004;17(2):259–275. doi: 10.1079/NRR200479.

106. Srinivasjois R, Rao S, Patole S. Prebiotic supplementation in preterm neonates: Updated systematic review and meta-analysis of randomised controlled trials. Clin Nutr. 2013;32(6):958–965. doi: 10.1016/j.clnu.2013.05.009.

107. Foolad N, Brezinski EA, Chase EP, Armstrong AW. Effect of nutrient supplementation on atopic dermatitis in children: a systematic review of probiotics, prebiotics, formula, and fatty acids JAMA Dermatol. 2013;149(3):350–355. doi: 10.1001/jamadermatol.2013.1495.

108. Osborn DA, Sinn JK. Prebiotics in infants for prevention of allergy. Cochrane Database Syst Rev. 2013;(3):CD006474. doi: 10.1002/14651858.CD006474.pub3.

109. Rao S, Srinivasjois R, Patole S. Prebiotic supplementation in full-term neonates: a systematic review of randomized controlled trials. Arch Pediatr Adolesc Med. 2009;163(8):755–764. doi: 10.1001/archpediatrics.2009.94.

110. Arslanoglu S, Moro GE, Schmitt J, et al. Early dietary intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestations and infections during the first two years of life. J Nutr. 2008;138(6):1091–1095. doi: 10.1093/jn/138.6.1091.

111. Schouten B, Van Esch BC, Kormelink TG, et al. Nondigestible oligosaccharides reduce immunoglobulin free light-chain concentrations in infants at risk for allergy. Pediatr Allergy Immunol. 2011;22(5):537–542. doi: 10.1111/j.1399-3038.2010.01132.x.

112. Boyle RJ, Tang ML, Chiang WC, et al.; PATCH study investigators. 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):701–710. doi: 10.1111/all.12848.

113. Wopereis H, Sim K, Shaw A, et al. Intestinal microbiota in infants at high risk for allergy: effects of prebiotics and role in eczema development. J Allergy Clin Immunol. 2018;141(4):1334–1342. e5. doi: 10.1016/j.jaci.2017.05.054.

114. Макарова Е.Г., Нетребенко О.К., Украинцев С.Е. Олигосахариды грудного молока: история открытия, структура и защитные функции // Педиатрия. Журнал им. Г.Н. Сперанского. — 2018. — Т.97. — №4. — С. 152–160. doi: 10.24110/0031-403x-2018-97-4-152-160.

115. West CE, Dzidic M, Prescott SL, Jenmalm MC. Bugging allergy; role of pre-, pro- and synbiotics in allergy prevention. Allergol Int. 2017;66(4):529–538. doi: 10.1016/j.alit.2017.08.001.

116. Lundelin K, Poussa T, Salminen S, Isolauri E. Long-term safety and efficacy of perinatal probiotic intervention: evidence from a follow-up study of four randomized, double-blind, placebocontrolled trials. Pediatr Allergy Immunol. 2017;28(2):170–175. doi: 10.1111/pai.12675.