Влияние кишечной микробиоты на иммунную систему ребенка в первую тысячу дней жизни и возможности пробиотической коррекции

1. Fusunyan R, Nanthakumar N, Baldeon M, Walker W. Evidence for an innate immune response in the immature human intestine: toll-like receptors on fetal enterocytes. Pediatr Res 2001; 49 (4): 589–93.
2. Leeansyah E, Loh L, Nixon D, Sandberg J. Acquisition of innate-like microbial reactivity in mucosal tissues during human fetal MAIT-cell development. Nat Commun 2014; 5: 3143.
3. Jiménez E, Marín M, Martín R et al. Is meconium from healthy newborns actually sterile? Res Microbiol 2008; 159 (3): 187–93.
4. Hu J, Nomura Y, Bashir A et al. Diversified Microbiota of Meconium Is Affected by Maternal Diabetes Status. PLoS ONE 2013; 8 (11): e78257.
5. Ardissone A, de la Cruz D, Davis-Richardson A et al. Meconium Microbiome Analysis Identifies Bacteria Correlated with Premature Birth. PLoS ONE 2014; 9 (3): e90784.
6. Collado M, Rautava S, Aakko J et al. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci Rep 2016; 6 (1).
7. Onderdonk A, Hecht J, McElrath T et al. Colonization of second-trimester placenta parenchyma. Am J Obst Gynecol 2008; 199 (1): 52.
8. Aagaard K, Ma J, Antony K et al. The Placenta Harbors a Unique Microbiome. Sci Translational Med 2014; 6 (237): 237.
9. Pal C, Bengtsson-Palme J, Kristiansson E, Larsson D. The structure and diversity of human, animal and environmental resistomes. Microbiome 2016; 4 (1).
10. Shiozaki A, Yoneda S, Yoneda N et al. Intestinal Microbiota is Different in Women with Preterm Birth: Results from Terminal Restriction Fragment Length Polymorphism Analysis. PLoS ONE 2014; 9 (11): e111374.
11. Neu J. The microbiome during pregnancy and early postnatal life. Seminars in Fetal and Neonatal Medicine. 2016; 21 (6): 373–9.
12. Madan J, Salari R, Saxena D et al. Gut microbial colonisation in premature neonates predicts neonatal sepsis. Arch Dis Child Fetal Neonatal Ed 2012; 97 (6): F456–F462.
13. Koleva P, Kim J, Scott J, Kozyrskyj A. Microbial programming of health and disease starts during fetal life. Birth Defects Res C Embryo Today 2015; 105 (4): 265–77.
14. Gosalbes M, Llop S, Vallès Y et al. Meconium microbiota types dominated by lactic acid or enteric bacteria are differentially associated with maternal eczema and respiratory problems in infants. Clin Experim Allergy 2013; 43 (2): 198–211.
15. Metsälä J, Lundqvist A, Virta LJ et al. Mother’s and offspring’s use of antibiotics and infant allergy to cow’s milk. Epidemiology 2013; 24 (2): 303–9.
16. Dogra S, Sakwinska O, Soh S et al. Dynamics of Infant Gut Microbiota Are Influenced by Delivery Mode and Gestational Duration and Are Associated with Subsequent Adiposity. mBio 2015; 6 (1): e02419–14.
17. Collado M, Isolauri E, Laitinen K et al. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr 2008; 88 (4): 894–9.
18. Abrahamsson T, Jakobsson T, Böttcher M et al. Probiotics in prevention of IgE-associated eczema: A double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 2007; 119 (5): 1174–80.
19. Kalliomäki M, Salminen S, Poussa H et al. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 2003; 361 (9372): 1869–71.
20. Dominguez-Bello M, Costello E, Contreras M et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proceed Nat Acad Sci 2010; 107 (26): 11971–5.
21. Roduit C, Scholtens S, de Jongste J et al. Asthma at 8 years of age in children born by caesarean section. Thorax 2009; 64 (2): 107–13.
22. Bonifacio E, Warncke K, Winkler C et al. Cesarean section and interferon-induced helicase gene polymorphisms combine to increase childhood type 1 diabetes risk. Diabetes 2011; 60 (12): 3300–6.
23. Marild K, Stephansson O, Montgomery S et al. Pregnancy outcome and risk of celiac disease in offspring: a nationwide case-control study. Gastroenterology 2012; 142 (1): 39–45.
24. Rautava S, Luoto R, Salminen S, Isolauri E. Microbial contact during pregnancy, intestinal colonization and human disease. Nat Rev Gastroenterol Hepatol 2012; 9 (10): 565.
25. Mueller N, Bakacs E, Combellick J et al. The infant microbiome development: mom matters. Trends Molecular Medicine 2015; 21 (2): 109–17.
26. Risnes K, Belanger K, Murk W et al. Antibiotic Exposure by 6 Months and Asthma and Allergy at 6 Years: Findings in a Cohort of 1,401 US Children. Am J Epidemiology 2010; 173 (3): 310–8.
27. Chu D, Ma J, Prince A et al. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nature Medicine 2017; 23 (3): 314–26.
28. Fouhy F, Guinane C, 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): 5811–20.
29. 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): 80–7.
30. Azad M, Konya T, Persaud R et al. Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study. BJOG 2015; 123 (6): 983–93.
31. Martin R, Makino H, Yavuz A et al. Early-life events, including mode of delivery and type of feeding, siblings and gender, shape the developing gut microbiota. PLoS One 2016; 11 (6): e0158498.
32. Fan W, Huo G, Li X et al. Diversity of the intestinal microbiota in different patterns of feeding infants by Illumina high-throughput sequencing. World J Microbiol Biotechnol 2013; 29 (12): 2365–72.
33. Lee S, Lim J, Kim B et al. Comparison of the gut microbiota profile in breastfed and formula-fed Korean infants using pyrosequencing. Nutrition Res Practice 2015; 9 (3): 242–8.
34. Thompson A, Monteagudo-Mera A, Cadenas M et al. Milk- and solid-feeding practices and daycare attendance are associated with differences in bacterial diversity, predominant communities, and metabolic and immune function of the infant gut microbiome. Front Cell Infect Microbiol 2015; 5: 3.
35. Magne F, Hachelaf W, Suau A et al. A longitudinal study of infant faecal microbiota during weaning. FEMS Microbiol Ecol 2006; 58 (3): 563–71.
36. Bezirtzoglou E, Tsiotsias A, Welling G. Microbiota profile in feces of breast- and formula-fed newborns by using fluorescence in situ hybridization (FISH). Anaerobe 2011; 17 (6): 478–82.
37. Turroni F, Peano C, Pass D et al. Diversity of Bifidobacteria within the Infant Gut Microbiota. PLoS ONE 2012; 7 (5): e36957.
38. Davis E, Wang M, Donovan S. The role of early life nutrition in the establishment of gastrointestinal microbial composition and function. Gut Microbes 2017; 8 (2): 143–71.
39. Backhed F, Roswall J, Peng Y et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 2015; 17 (6): 852.
40. Bergstrom A, Skov T, Bahl M et al. Establishment of intestinal microbiota during early life: a longitudinal, explorative study of a large cohort of Danish infants. Appl Environ Microbiol 2014; 80 (9): 2889–900.
41. Valles Y, Artacho A, Pascual-Garcıa A et al. Microbial succession in the gut: directional trends of taxonomic and functional change in a birth cohort of Spanish infants. PLoS Genet 2014; 10 (6): e1004406.
42. Koenig J, Spor A, Scalfone N et al. Succession of microbial consortia in the developing infant gut microbiome. Proceed Nat Acad Sci 2011; 108 (1): 4578–85.
43. Walker W. Bacterial Colonization of the Newborn Gut, Immune Development, and Prevention of Disease. Nestle Nutr Inst Workshop Ser 2017; 88: 23–33.
44. Bisgaard H, Li N, Bonnelykke K et al. Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. 
J Allergy Clin Immunol 2011; 128 (3): 646–52.
45. Abrahamsson T, Jakobsson H, Andersson A et al. Low diversity of the gut microbiota in infants with atopic eczema. J Allergy Clin Immunol 2012; 129 (2): 434–40.
46. Ismail I, Oppedisano F, Joseph S. et al. Reduced gut microbial diversity in early life is associated with later development of eczema but not atopy in high-risk infants. Pediatric Allergy Immunol 2012; 23 (7): 674–81.
47. Sjögren Y, Jenmalm M, Böttcher M et al. Altered early infant gut microbiota in children developing allergy up to 5 years of age. Clinical Experim Allergy 2009; 39 (4): 518–26.
48. Johansson M, Sjögren Y, Persson J et al. Early Colonization with a Group of Lactobacilli Decreases the Risk for Allergy at Five Years of Age Despite Allergic Heredity. PLoS ONE 2011; 6 (8): e23031.
49. Szajewska H, Setty M, Mrukowicz J, Guandalini S. Probiotics in gastrointestinal diseases in children: hard and not-so-hard evidence of efficacy. J Pediatric Gastroenterol Nutrition 2006; 42: 454–75.
50. Sazawal S, Dhingra U, Sarkar A et al. Efficacy of milk fortified with a probiotic Bifidobacterium lactis (DR-10TM) and prebiotic galactooligosaccharides in prevention of morbidity and on nutritional status. Asia Pacific J Clin Nutrition 2004; 13: 28.
51. Alfaleh K, Bassler D. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Evidence‐Based Child Health Cochrane Rev J 2012; 7 (6): 1807–54.
52. 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 (9573): 1614–20.
53. Hunter C, Dimaguila M, Gal P et al. Effect of routine probiotic, Lactobacillus reuteri DSM 17938, use on rates of necrotizing enterocolitis in neonates with birthweight 1000 grams: a sequential analysis. BMC Pediatr 2012; 12 (1): 142.
54. Mattar A, Drongowski R, Coran A et al. Effect of probiotics on enterocyte bacterial translocation in vitro. Ped Surg Int 2001; 17 (4): 265–8.
55. Reid G, Howard J, Gan B. Can bacterial interference prevent infection? Trends Microbiol 2001; 9 (9): 424–8.
56. Martin C, Walker W. Probiotics: role in pathophysiology and prevention in necrotizing enterocolitis. Semin Perinatol 2008; 32 (2): 127–37.

________________________________________________

1. Fusunyan R, Nanthakumar N, Baldeon M, Walker W. Evidence for an innate immune response in the immature human intestine: toll-like receptors on fetal enterocytes. Pediatr Res 2001; 49 (4): 589–93.
2. Leeansyah E, Loh L, Nixon D, Sandberg J. Acquisition of innate-like microbial reactivity in mucosal tissues during human fetal MAIT-cell development. Nat Commun 2014; 5: 3143.
3. Jiménez E, Marín M, Martín R et al. Is meconium from healthy newborns actually sterile? Res Microbiol 2008; 159 (3): 187–93.
4. Hu J, Nomura Y, Bashir A et al. Diversified Microbiota of Meconium Is Affected by Maternal Diabetes Status. PLoS ONE 2013; 8 (11): e78257.
5. Ardissone A, de la Cruz D, Davis-Richardson A et al. Meconium Microbiome Analysis Identifies Bacteria Correlated with Premature Birth. PLoS ONE 2014; 9 (3): e90784.
6. Collado M, Rautava S, Aakko J et al. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci Rep 2016; 6 (1).
7. Onderdonk A, Hecht J, McElrath T et al. Colonization of second-trimester placenta parenchyma. Am J Obst Gynecol 2008; 199 (1): 52.
8. Aagaard K, Ma J, Antony K et al. The Placenta Harbors a Unique Microbiome. Sci Translational Med 2014; 6 (237): 237.
9. Pal C, Bengtsson-Palme J, Kristiansson E, Larsson D. The structure and diversity of human, animal and environmental resistomes. Microbiome 2016; 4 (1).
10. Shiozaki A, Yoneda S, Yoneda N et al. Intestinal Microbiota is Different in Women with Preterm Birth: Results from Terminal Restriction Fragment Length Polymorphism Analysis. PLoS ONE 2014; 9 (11): e111374.
11. Neu J. The microbiome during pregnancy and early postnatal life. Seminars in Fetal and Neonatal Medicine. 2016; 21 (6): 373–9.
12. Madan J, Salari R, Saxena D et al. Gut microbial colonisation in premature neonates predicts neonatal sepsis. Arch Dis Child Fetal Neonatal Ed 2012; 97 (6): F456–F462.
13. Koleva P, Kim J, Scott J, Kozyrskyj A. Microbial programming of health and disease starts during fetal life. Birth Defects Res C Embryo Today 2015; 105 (4): 265–77.
14. Gosalbes M, Llop S, Vallès Y et al. Meconium microbiota types dominated by lactic acid or enteric bacteria are differentially associated with maternal eczema and respiratory problems in infants. Clin Experim Allergy 2013; 43 (2): 198–211.
15. Metsälä J, Lundqvist A, Virta LJ et al. Mother’s and offspring’s use of antibiotics and infant allergy to cow’s milk. Epidemiology 2013; 24 (2): 303–9.
16. Dogra S, Sakwinska O, Soh S et al. Dynamics of Infant Gut Microbiota Are Influenced by Delivery Mode and Gestational Duration and Are Associated with Subsequent Adiposity. mBio 2015; 6 (1): e02419–14.
17. Collado M, Isolauri E, Laitinen K et al. Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am J Clin Nutr 2008; 88 (4): 894–9.
18. Abrahamsson T, Jakobsson T, Böttcher M et al. Probiotics in prevention of IgE-associated eczema: A double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 2007; 119 (5): 1174–80.
19. Kalliomäki M, Salminen S, Poussa H et al. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 2003; 361 (9372): 1869–71.
20. Dominguez-Bello M, Costello E, Contreras M et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proceed Nat Acad Sci 2010; 107 (26): 11971–5.
21. Roduit C, Scholtens S, de Jongste J et al. Asthma at 8 years of age in children born by caesarean section. Thorax 2009; 64 (2): 107–13.
22. Bonifacio E, Warncke K, Winkler C et al. Cesarean section and interferon-induced helicase gene polymorphisms combine to increase childhood type 1 diabetes risk. Diabetes 2011; 60 (12): 3300–6.
23. Marild K, Stephansson O, Montgomery S et al. Pregnancy outcome and risk of celiac disease in offspring: a nationwide case-control study. Gastroenterology 2012; 142 (1): 39–45.
24. Rautava S, Luoto R, Salminen S, Isolauri E. Microbial contact during pregnancy, intestinal colonization and human disease. Nat Rev Gastroenterol Hepatol 2012; 9 (10): 565.
25. Mueller N, Bakacs E, Combellick J et al. The infant microbiome development: mom matters. Trends Molecular Medicine 2015; 21 (2): 109–17.
26. Risnes K, Belanger K, Murk W et al. Antibiotic Exposure by 6 Months and Asthma and Allergy at 6 Years: Findings in a Cohort of 1,401 US Children. Am J Epidemiology 2010; 173 (3): 310–8.
27. Chu D, Ma J, Prince A et al. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nature Medicine 2017; 23 (3): 314–26.
28. Fouhy F, Guinane C, 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): 5811–20.
29. 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): 80–7.
30. Azad M, Konya T, Persaud R et al. Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study. BJOG 2015; 123 (6): 983–93.
31. Martin R, Makino H, Yavuz A et al. Early-life events, including mode of delivery and type of feeding, siblings and gender, shape the developing gut microbiota. PLoS One 2016; 11 (6): e0158498.
32. Fan W, Huo G, Li X et al. Diversity of the intestinal microbiota in different patterns of feeding infants by Illumina high-throughput sequencing. World J Microbiol Biotechnol 2013; 29 (12): 2365–72.
33. Lee S, Lim J, Kim B et al. Comparison of the gut microbiota profile in breastfed and formula-fed Korean infants using pyrosequencing. Nutrition Res Practice 2015; 9 (3): 242–8.
34. Thompson A, Monteagudo-Mera A, Cadenas M et al. Milk- and solid-feeding practices and daycare attendance are associated with differences in bacterial diversity, predominant communities, and metabolic and immune function of the infant gut microbiome. Front Cell Infect Microbiol 2015; 5: 3.
35. Magne F, Hachelaf W, Suau A et al. A longitudinal study of infant faecal microbiota during weaning. FEMS Microbiol Ecol 2006; 58 (3): 563–71.
36. Bezirtzoglou E, Tsiotsias A, Welling G. Microbiota profile in feces of breast- and formula-fed newborns by using fluorescence in situ hybridization (FISH). Anaerobe 2011; 17 (6): 478–82.
37. Turroni F, Peano C, Pass D et al. Diversity of Bifidobacteria within the Infant Gut Microbiota. PLoS ONE 2012; 7 (5): e36957.
38. Davis E, Wang M, Donovan S. The role of early life nutrition in the establishment of gastrointestinal microbial composition and function. Gut Microbes 2017; 8 (2): 143–71.
39. Backhed F, Roswall J, Peng Y et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 2015; 17 (6): 852.
40. Bergstrom A, Skov T, Bahl M et al. Establishment of intestinal microbiota during early life: a longitudinal, explorative study of a large cohort of Danish infants. Appl Environ Microbiol 2014; 80 (9): 2889–900.
41. Valles Y, Artacho A, Pascual-Garcıa A et al. Microbial succession in the gut: directional trends of taxonomic and functional change in a birth cohort of Spanish infants. PLoS Genet 2014; 10 (6): e1004406.
42. Koenig J, Spor A, Scalfone N et al. Succession of microbial consortia in the developing infant gut microbiome. Proceed Nat Acad Sci 2011; 108 (1): 4578–85.
43. Walker W. Bacterial Colonization of the Newborn Gut, Immune Development, and Prevention of Disease. Nestle Nutr Inst Workshop Ser 2017; 88: 23–33.
44. Bisgaard H, Li N, Bonnelykke K et al. Reduced diversity of the intestinal microbiota during infancy is associated with increased risk of allergic disease at school age. 
J Allergy Clin Immunol 2011; 128 (3): 646–52.
45. Abrahamsson T, Jakobsson H, Andersson A et al. Low diversity of the gut microbiota in infants with atopic eczema. J Allergy Clin Immunol 2012; 129 (2): 434–40.
46. Ismail I, Oppedisano F, Joseph S. et al. Reduced gut microbial diversity in early life is associated with later development of eczema but not atopy in high-risk infants. Pediatric Allergy Immunol 2012; 23 (7): 674–81.
47. Sjögren Y, Jenmalm M, Böttcher M et al. Altered early infant gut microbiota in children developing allergy up to 5 years of age. Clinical Experim Allergy 2009; 39 (4): 518–26.
48. Johansson M, Sjögren Y, Persson J et al. Early Colonization with a Group of Lactobacilli Decreases the Risk for Allergy at Five Years of Age Despite Allergic Heredity. PLoS ONE 2011; 6 (8): e23031.
49. Szajewska H, Setty M, Mrukowicz J, Guandalini S. Probiotics in gastrointestinal diseases in children: hard and not-so-hard evidence of efficacy. J Pediatric Gastroenterol Nutrition 2006; 42: 454–75.
50. Sazawal S, Dhingra U, Sarkar A et al. Efficacy of milk fortified with a probiotic Bifidobacterium lactis (DR-10TM) and prebiotic galactooligosaccharides in prevention of morbidity and on nutritional status. Asia Pacific J Clin Nutrition 2004; 13: 28.
51. Alfaleh K, Bassler D. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Evidence‐Based Child Health Cochrane Rev J 2012; 7 (6): 1807–54.
52. 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 (9573): 1614–20.
53. Hunter C, Dimaguila M, Gal P et al. Effect of routine probiotic, Lactobacillus reuteri DSM 17938, use on rates of necrotizing enterocolitis in neonates with birthweight 1000 grams: a sequential analysis. BMC Pediatr 2012; 12 (1): 142.
54. Mattar A, Drongowski R, Coran A et al. Effect of probiotics on enterocyte bacterial translocation in vitro. Ped Surg Int 2001; 17 (4): 265–8.
55. Reid G, Howard J, Gan B. Can bacterial interference prevent infection? Trends Microbiol 2001; 9 (9): 424–8.
56. Martin C, Walker W. Probiotics: role in pathophysiology and prevention in necrotizing enterocolitis. Semin Perinatol 2008; 32 (2): 127–37.

А.С.Якушин1,2, М.Ю.Денисов*2

1 ООО «Центр семейной медицины». 630090, Россия, Новосибирск, ул. Пирогова, д. 25/4;
2 ФГАОУ ВО «Новосибирский национальный исследовательский государственный университет». 
630090, Россия, Новосибирск, ул. Пирогова, д. 1
*mi.den@mail.ru

________________________________________________

A.S.Yakushin1,2, M.Yu.Denisov*2

1 Family Medicine Center. 630090, Russian Federation, Novosibirsk, ul. Pirogova, d. 25/4;
2 Novosibirsk National Research State University. 630090, Russian Federation, Novosibirsk, ul. Pirogova, d. 1
*mi.den@mail.ru