Semin Reprod Med 2014; 32(01): 074-086
DOI: 10.1055/s-0033-1361825
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Early Development of the Gut Microbiome and Immune-Mediated Childhood Disorders

Min Li
1   Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois
,
Mei Wang
1   Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois
,
Sharon M. Donovan
1   Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2014 (online)

Abstract

The human gastrointestinal tract inhabits a complex microbial ecosystem that plays a vital role in host health through its contributions to nutrient synthesis and digestion, protection from pathogens, and promoting maturation of host innate and adapt immune systems. The development of gut microbiota primarily occurs during infancy and is influenced by multiple factors, including prenatal exposure; gestational age; mode of delivery; feeding type; pre-, pro-, and antibiotic use; and host genetics. In genetically susceptible individuals, changes in the gut microbiota induced by environmental factors may contribute to the development of immune-related disorders in childhood, including atopic diseases, inflammatory bowel disease, irritable bowel syndrome, and necrotizing enterocolitis. Pre- and probiotics may be useful in the prevention and treatment of some immune-related diseases by modulating gut microbiota and regulating host mucosal immune function. The review will discuss recent findings on the environmental factors that influence development of gut microbiota during infancy and its potential impact on some immune-related diseases in childhood. The use of pre- and probiotics for prevention and intervention of several important diseases in early life will also be reviewed.

 
  • References

  • 1 Rautava S, Isolauri E. The development of gut immune responses and gut microbiota: effects of probiotics in prevention and treatment of allergic disease. Curr Issues Intest Microbiol 2002; 3 (1) 15-22
  • 2 Donovan S. Role of human milk components in gastrointestinal development: Current knowledge and future NEEDS. J Pediatr 2006; 149 (5) S49-S61
  • 3 Field CJ. The immunological components of human milk and their effect on immune development in infants. J Nutr 2005; 135 (1) 1-4
  • 4 Azad MB, Kozyrskyj AL. Perinatal programming of asthma: the role of gut microbiota. Clin Dev Immunol 2012; 2012: 932072
  • 5 Forchielli ML, Walker WA. The role of gut-associated lymphoid tissues and mucosal defence. Br J Nutr 2005; 93 (Suppl. 01) S41-S48
  • 6 Dupaul-Chicoine J, Dagenais M, Saleh M. Crosstalk between the intestinal microbiota and the innate immune system in intestinal homeostasis and inflammatory bowel disease. Inflamm Bowel Dis 2013; 19 (10) 2227-2237
  • 7 Mackie RI, Sghir A, Gaskins HR. Developmental microbial ecology of the neonatal gastrointestinal tract. Am J Clin Nutr 1999; 69 (5) 1035S-1045S
  • 8 Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO. Development of the human infant intestinal microbiota. PLoS Biol 2007; 5 (7) e177
  • 9 Iebba V, Aloi M, Civitelli F, Cucchiara S. Gut microbiota and pediatric disease. Dig Dis 2011; 29 (6) 531-539
  • 10 Weber TK, Polanco I. Gastrointestinal microbiota and some children diseases: a review. Gastroenterol Res Pract 2012; 2012: 676585
  • 11 Snyder M. The bacterial flora of meconium specimens collected from sixty-four infants within four hours after delivery. J Pediatr 1936; 9 (5) 624-632
  • 12 Jiménez E, Marín ML, Martín R , et al. Is meconium from healthy newborns actually sterile?. Res Microbiol 2008; 159 (3) 187-193
  • 13 DiGiulio DB. Diversity of microbes in amniotic fluid. Semin Fetal Neonatal Med 2012; 17 (1) 2-11
  • 14 DiGiulio DB, Romero R, Amogan HP , et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS ONE 2008; 3 (8) e3056
  • 15 Steel JH, Malatos S, Kennea N , et al. Bacteria and inflammatory cells in fetal membranes do not always cause preterm labor. Pediatr Res 2005; 57 (3) 404-411
  • 16 Jiménez E, Fernández L, Marín ML , et al. Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean section. Curr Microbiol 2005; 51 (4) 270-274
  • 17 Satokari R, Grönroos T, Laitinen K, Salminen S, Isolauri E. Bifidobacterium and Lactobacillus DNA in the human placenta. Lett Appl Microbiol 2009; 48 (1) 8-12
  • 18 Pettker CM, Buhimschi IA, Magloire LK, Sfakianaki AK, Hamar BD, Buhimschi CS. Value of placental microbial evaluation in diagnosing intra-amniotic infection. Obstet Gynecol 2007; 109 (3) 739-749
  • 19 Martin R, Langa S, Reviriego C , et al. The commensal microflora of human milk: New perspectives for food bacteriotherapy and probiotics. Trends Food Sci Technol 2004; 14: 121-127
  • 20 Thum C, Cookson AL, Otter DE , et al. Can nutritional modulation of maternal intestinal microbiota influence the development of the infant gastrointestinal tract?. J Nutr 2012; 142 (11) 1921-1928
  • 21 Bearfield C, Davenport ES, Sivapathasundaram V, Allaker RP. Possible association between amniotic fluid micro-organism infection and microflora in the mouth. BJOG 2002; 109 (5) 527-533
  • 22 Wagner CL, Taylor SN, Johnson D. Host factors in amniotic fluid and breast milk that contribute to gut maturation. Clin Rev Allergy Immunol 2008; 34 (2) 191-204
  • 23 Blakey JL, Lubitz L, Barnes GL, Bishop RF, Campbell NT, Gillam GL. Development of gut colonisation in pre-term neonates. J Med Microbiol 1982; 15 (4) 519-529
  • 24 Magne F, Abély M, Boyer F, Morville P, Pochart P, Suau A. Low species diversity and high interindividual variability in faeces of preterm infants as revealed by sequences of 16S rRNA genes and PCR-temporal temperature gradient gel electrophoresis profiles. FEMS Microbiol Ecol 2006; 57 (1) 128-138
  • 25 Sakata H, Yoshioka H, Fujita K. Development of the intestinal flora in very low birth weight infants compared to normal full-term newborns. Eur J Pediatr 1985; 144 (2) 186-190
  • 26 Gewolb IH, Schwalbe RS, Taciak VL, Harrison TS, Panigrahi P. Stool microflora in extremely low birthweight infants. Arch Dis Child Fetal Neonatal Ed 1999; 80 (3) F167-F173
  • 27 Westerbeek EA, van den Berg A, Lafeber HN, Knol J, Fetter WP, van Elburg RM. The intestinal bacterial colonisation in preterm infants: a review of the literature. Clin Nutr 2006; 25 (3) 361-368
  • 28 Butel MJ, Suau A, Campeotto F , et al. Conditions of bifidobacterial colonization in preterm infants: a prospective analysis. J Pediatr Gastroenterol Nutr 2007; 44 (5) 577-582
  • 29 Jacquot A, Neveu D, Aujoulat F , et al. Dynamics and clinical evolution of bacterial gut microflora in extremely premature patients. J Pediatr 2011; 158 (3) 390-396
  • 30 Scholtens PA, Oozeer R, Martin R, Amor KB, Knol J. The early settlers: intestinal microbiology in early life. Annu Rev Food Sci Technol 2012; 3: 425-447
  • 31 Claud EC, Walker WA. Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis. FASEB J 2001; 15 (8) 1398-1403
  • 32 Mai V, Young CM, Ukhanova M , et al. Fecal microbiota in premature infants prior to necrotizing enterocolitis. PLoS ONE 2011; 6 (6) e20647
  • 33 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) 11971-11975
  • 34 Biasucci G, Benenati B, Morelli L, Bessi E, Boehm G. Cesarean delivery may affect the early biodiversity of intestinal bacteria. J Nutr 2008; 138 (9) 1796S-1800S
  • 35 Penders J, Thijs C, Vink C , et al. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics 2006; 118 (2) 511-521
  • 36 Harmsen HJ, Wildeboer-Veloo AC, Raangs GC , et al. Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. J Pediatr Gastroenterol Nutr 2000; 30 (1) 61-67
  • 37 Yatsunenko T, Rey FE, Manary MJ , et al. Human gut microbiome viewed across age and geography. Nature 2012; 486 (7402) 222-227
  • 38 Adlerberth I, Wold AE. Establishment of the gut microbiota in Western infants. Acta Paediatr 2009; 98 (2) 229-238
  • 39 Kunz C, Rudloff S, Baier W, Klein N, Strobel S. Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annu Rev Nutr 2000; 20: 699-722
  • 40 Martín-Sosa S, Martín MJ, García-Pardo LA, Hueso P. Sialyloligosaccharides in human and bovine milk and in infant formulas: variations with the progression of lactation. J Dairy Sci 2003; 86 (1) 52-59
  • 41 Marcobal A, Barboza M, Froehlich JW , et al. Consumption of human milk oligosaccharides by gut-related microbes. J Agric Food Chem 2010; 58 (9) 5334-5340
  • 42 Marcobal A, Barboza M, Sonnenburg ED , et al. Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways. Cell Host Microbe 2011; 10 (5) 507-514
  • 43 Fernández L, Langa S, Martín V , et al. The human milk microbiota: origin and potential roles in health and disease. Pharmacol Res 2013; 69 (1) 1-10
  • 44 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. 01) 4578-4585
  • 45 Fallani M, Amarri S, Uusijarvi A , et al; INFABIO team. Determinants of the human infant intestinal microbiota after the introduction of first complementary foods in infant samples from five European centres. Microbiology 2011; 157 (Pt 5) 1385-1392
  • 46 Roberfroid M, Gibson GR, Hoyles L , et al. Prebiotic effects: metabolic and health benefits. Br J Nutr 2010; 104 (Suppl. 02) S1-S63
  • 47 Haarman M, Knol J. Quantitative real-time PCR assays to identify and quantify fecal Bifidobacterium species in infants receiving a prebiotic infant formula. Appl Environ Microbiol 2005; 71 (5) 2318-2324
  • 48 Veereman G. Pediatric applications of inulin and oligofructose. J Nutr 2007; 137 (11, Suppl): 2585S-2589S
  • 49 Salvini F, Riva E, Salvatici E , et al. A specific prebiotic mixture added to starting infant formula has long-lasting bifidogenic effects. J Nutr 2011; 141 (7) 1335-1339
  • 50 Shadid R, Haarman M, Knol J , et al. Effects of galactooligosaccharide and long-chain fructooligosaccharide supplementation during pregnancy on maternal and neonatal microbiota and immunity—a randomized, double-blind, placebo-controlled study. Am J Clin Nutr 2007; 86 (5) 1426-1437
  • 51 Food and Agriculture Organization/World Health Organization. Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria. 2001 . Available at: http://www.who.int/foodsafety/publications/s_management/probiotics/en/ . Accessed on December 3, 2013
  • 52 Grześkowiak L, Grönlund MM, Beckmann C, Salminen S, von Berg A, Isolauri E. The impact of perinatal probiotic intervention on gut microbiota: double-blind placebo-controlled trials in Finland and Germany. Anaerobe 2012; 18 (1) 7-13
  • 53 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
  • 54 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
  • 55 Van de Merwe JP, Stegeman JH, Hazenberg MP. The resident faecal flora is determined by genetic characteristics of the host. Implications for Crohn's disease?. Antonie van Leeuwenhoek 1983; 49 (2) 119-124
  • 56 Stewart JA, Chadwick VS, Murray A. Investigations into the influence of host genetics on the predominant eubacteria in the faecal microflora of children. J Med Microbiol 2005; 54 (Pt 12) 1239-1242
  • 57 Zoetendal EG, Akkermans ADL, Akkermans-van Vliet WM, de Visser JAGM, de Vos WM. The host genotype affects the bacterial community in the human gastrointestinal tract. Microb Ecol Health Dis 2001; 13 (3) 129-134
  • 58 Turnbaugh PJ, Hamady M, Yatsunenko T , et al. A core gut microbiome in obese and lean twins. Nature 2009; 457 (7228) 480-484
  • 59 Benson AK, Kelly SA, Legge R , et al. Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors. Proc Natl Acad Sci U S A 2010; 107 (44) 18933-18938
  • 60 McKnite AM, Perez-Munoz ME, Lu L , et al. Murine gut microbiota is defined by host genetics and modulates variation of metabolic traits. PLoS ONE 2012; 7 (6) e39191
  • 61 Kaplan JL, Shi HN, Walker WA. The role of microbes in developmental immunologic programming. Pediatr Res 2011; 69 (6) 465-472
  • 62 Vael C, Desager K. The importance of the development of the intestinal microbiota in infancy. Curr Opin Pediatr 2009; 21 (6) 794-800
  • 63 Murgas Torrazza R, Neu J. The developing intestinal microbiome and its relationship to health and disease in the neonate. J Perinatol 2011; 31 (Suppl. 01) S29-S34
  • 64 Lai CK, Beasley R, Crane J, Foliaki S, Shah J, Weiland S ; International Study of Asthma and Allergies in Childhood Phase Three Study Group. Global variation in the prevalence and severity of asthma symptoms: phase three of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax 2009; 64 (6) 476-483
  • 65 Mannino DM, Homa DM, Pertowski CA , et al. Surveillance for asthma—United States, 1960-1995. MMWR CDC Surveill Summ 1998; 47 (1) 1-27
  • 66 Beasley R, Crane J, Lai CK, Pearce N. Prevalence and etiology of asthma. J Allergy Clin Immunol 2000; 105 (2, Pt 2) S466-S472
  • 67 Asher MI, Keil U, Anderson HR , et al. International study of asthma and allergies in childhood (ISAAC): rationale and methods. Eur Respir J 1995; 8 (3) 483-491
  • 68 Strachan DP. Hay fever, hygiene, and household size. BMJ 1989; 299 (6710) 1259-1260
  • 69 Björkstén B, Naaber P, Sepp E, Mikelsaar M. The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin Exp Allergy 1999; 29 (3) 342-346
  • 70 Fukuda S, Ishikawa H, Koga Y , et al. Allergic symptoms and microflora in schoolchildren. J Adolesc Health 2004; 35 (2) 156-158
  • 71 Kalliomäki M, Kirjavainen P, Eerola E, Kero P, Salminen S, Isolauri E. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing. J Allergy Clin Immunol 2001; 107 (1) 129-134
  • 72 Penders J, Thijs C, van den Brandt PA , et al. Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. Gut 2007; 56 (5) 661-667
  • 73 Rautava S, Kalliomäki M, Isolauri E. New therapeutic strategy for combating the increasing burden of allergic disease: Probiotics-A Nutrition, Allergy, Mucosal Immunology and Intestinal Microbiota (NAMI) Research Group report. J Allergy Clin Immunol 2005; 116 (1) 31-37
  • 74 Huffnagle GB. The microbiota and allergies/asthma. PLoS Pathog 2010; 6 (5) e1000549
  • 75 Noverr MC, Huffnagle GB. The 'microflora hypothesis' of allergic diseases. Clin Exp Allergy 2005; 35 (12) 1511-1520
  • 76 Vael C, Vanheirstraeten L, Desager KN, Goossens H. Denaturing gradient gel electrophoresis of neonatal intestinal microbiota in relation to the development of asthma. BMC Microbiol 2011; 11: 68-2180
  • 77 Thavagnanam S, Fleming J, Bromley A, Shields MD, Cardwell CR. A meta-analysis of the association between Caesarean section and childhood asthma. Clin Exp Allergy 2008; 38 (4) 629-633
  • 78 Bager P, Melbye M, Rostgaard K, Benn CS, Westergaard T. Mode of delivery and risk of allergic rhinitis and asthma. J Allergy Clin Immunol 2003; 111 (1) 51-56
  • 79 van Nimwegen FA, Penders J, Stobberingh EE , et al. Mode and place of delivery, gastrointestinal microbiota, and their influence on asthma and atopy. J Allergy Clin Immunol 2011; 128 (5) 948-955 , e1–e3
  • 80 Mai XM, Kull I, Wickman M, Bergström A. Antibiotic use in early life and development of allergic diseases: respiratory infection as the explanation. Clin Exp Allergy 2010; 40 (8) 1230-1237
  • 81 Jedrychowski W, Perera F, Maugeri U , et al. Wheezing and asthma may be enhanced by broad spectrum antibiotics used in early childhood. Concept and results of a pharmacoepidemiology study. J Physiol Pharmacol 2011; 62 (2) 189-195
  • 82 Russell SL, Gold MJ, Hartmann M , et al. Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. EMBO Rep 2012; 13 (5) 440-447
  • 83 Kull I, Melen E, Alm J , et al. Breast-feeding in relation to asthma, lung function, and sensitization in young schoolchildren. J Allergy Clin Immunol 2010; 125 (5) 1013-1019
  • 84 Kusunoki T, Morimoto T, Nishikomori R , et al. Breastfeeding and the prevalence of allergic diseases in schoolchildren: does reverse causation matter?. Pediatr Allergy Immunol 2010; 21 (1, Pt 1): 60-66
  • 85 Pohlabeln H, Mühlenbruch K, Jacobs S, Böhmann H. Frequency of allergic diseases in 2-year-old children in relationship to parental history of allergy and breastfeeding. J Investig Allergol Clin Immunol 2010; 20 (3) 195-200
  • 86 Wright AL, Holberg CJ, Taussig LM, Martinez F. Maternal asthma status alters relation of infant feeding to asthma in childhood. Adv Exp Med Biol 2000; 478: 131-137
  • 87 Grönlund MM, Gueimonde M, Laitinen K , et al. Maternal breast-milk and intestinal bifidobacteria guide the compositional development of the Bifidobacterium microbiota in infants at risk of allergic disease. Clin Exp Allergy 2007; 37 (12) 1764-1772
  • 88 Asher MI, Montefort S, Björkstén B , et al; ISAAC Phase Three Study Group. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006; 368 (9537) 733-743
  • 89 Shaw TE, Currie GP, Koudelka CW, Simpson EL. Eczema prevalence in the united states: Data from the 2003 national survey of children's health. J Invest Dermatol 2011; 131 (1) 67-73
  • 90 Gore C, Munro K, Lay C , et al. Bifidobacterium pseudocatenulatum is associated with atopic eczema: a nested case-control study investigating the fecal microbiota of infants. J Allergy Clin Immunol 2008; 121 (1) 135-140
  • 91 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
  • 92 Abrahamsson TR, Jakobsson HE, Andersson AF, Björkstén B, Engstrand L, Jenmalm MC. Low diversity of the gut microbiota in infants with atopic eczema. J Allergy Clin Immunol 2012; 129 (2) 434-440 , e1–e2
  • 93 Ismail IH, Oppedisano F, Joseph SJ , et al. 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
  • 94 Foliaki S, Pearce N, Björkstén B, Mallol J, Montefort S, von Mutius E ; International Study of Asthma and Allergies in Childhood Phase III Study Group. Antibiotic use in infancy and symptoms of asthma, rhinoconjunctivitis, and eczema in children 6 and 7 years old: International Study of Asthma and Allergies in Childhood Phase III. J Allergy Clin Immunol 2009; 124 (5) 982-989
  • 95 Greer FR, Sicherer SH, Burks AW ; American Academy of Pediatrics Committee on Nutrition; American Academy of Pediatrics Section on Allergy and Immunology. Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics 2008; 121 (1) 183-191
  • 96 Ip S, Chung M, Raman G , et al. Breastfeeding and maternal and infant health outcomes in developed countries. Evid Rep Technol Assess (Full Rep) 2007; (153) 1-186
  • 97 Flohr C, Nagel G, Weinmayr G, Kleiner A, Strachan DP, Williams HC ; ISAAC Phase Two Study Group. Lack of evidence for a protective effect of prolonged breastfeeding on childhood eczema: lessons from the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two. Br J Dermatol 2011; 165 (6) 1280-1289
  • 98 Giwercman C, Halkjaer LB, Jensen SM, Bønnelykke K, Lauritzen L, Bisgaard H. Increased risk of eczema but reduced risk of early wheezy disorder from exclusive breast-feeding in high-risk infants. J Allergy Clin Immunol 2010; 125 (4) 866-871
  • 99 Gigante G, Tortora A, Ianiro G , et al. Role of gut microbiota in food tolerance and allergies. Dig Dis 2011; 29 (6) 540-549
  • 100 Thompson-Chagoyan OC, Vieites JM, Maldonado J, Edwards C, Gil A. Changes in faecal microbiota of infants with cow's milk protein allergy—a Spanish prospective case-control 6-month follow-up study. Pediatr Allergy Immunol 2010; 21 (2, Pt 2): e394-e400
  • 101 Thompson-Chagoyan OC, Fallani M, Maldonado J , et al. Faecal microbiota and short-chain fatty acid levels in faeces from infants with cow's milk protein allergy. Int Arch Allergy Immunol 2011; 156 (3) 325-332
  • 102 Rodriguez B, Prioult G, Bibiloni R , et al. Germ-free status and altered caecal subdominant microbiota are associated with a high susceptibility to cow's milk allergy in mice. FEMS Microbiol Ecol 2011; 76 (1) 133-144
  • 103 Rodriguez B, Prioult G, Hacini-Rachinel F , et al. Infant gut microbiota is protective against cow's milk allergy in mice despite immature ileal T-cell response. FEMS Microbiol Ecol 2012; 79 (1) 192-202
  • 104 Keski-Nisula L, Karvonen A, Pfefferle PI, Renz H, Büchele G, Pekkanen J. Birth-related factors and doctor-diagnosed wheezing and allergic sensitization in early childhood. Allergy 2010; 65 (9) 1116-1125
  • 105 Koplin JJ, Martin PE, Tang MLK , et al. Do factors known to alter infant microbial exposures alter the risk of food allergy and eczema in a population-based infant study?. J Allergy Clin Immunol 2012; 129 (2, Suppl): ABC231
  • 106 Eggesbø M, Botten G, Stigum H, Nafstad P, Magnus P. Is delivery by cesarean section a risk factor for food allergy?. J Allergy Clin Immunol 2003; 112 (2) 420-426
  • 107 Eggesbø M, Botten G, Stigum H, Samuelsen SO, Brunekreef B, Magnus P. Cesarean delivery and cow milk allergy/intolerance. Allergy 2005; 60 (9) 1172-1173
  • 108 Carlisle EM, Morowitz MJ. The intestinal microbiome and necrotizing enterocolitis. Curr Opin Pediatr 2013; 25 (3) 382-387
  • 109 Grishin A, Papillon S, Bell B, Wang J, Ford HR. The role of the intestinal microbiota in the pathogenesis of necrotizing enterocolitis. Semin Pediatr Surg 2013; 22 (2) 69-75
  • 110 Mshvildadze M, Neu J, Shuster J, Theriaque D, Li N, Mai V. Intestinal microbial ecology in premature infants assessed with non-culture-based techniques. J Pediatr 2010; 156 (1) 20-25
  • 111 Normann E, Fahlén A, Engstrand L, Lilja HE. Intestinal microbial profiles in extremely preterm infants with and without necrotizing enterocolitis. Acta Paediatr 2013; 102 (2) 129-136
  • 112 Stewart CJ, Marrs EC, Magorrian S , et al. The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection. Acta Paediatr 2012; 101 (11) 1121-1127
  • 113 Comito D, Romano C. Dysbiosis in the pathogenesis of pediatric inflammatory bowel diseases. Int J Inflamm 2012; 2012: 687143
  • 114 Cucchiara S, Iebba V, Conte MP, Schippa S. The microbiota in inflammatory bowel disease in different age groups. Dig Dis 2009; 27 (3) 252-258
  • 115 Aomatsu T, Imaeda H, Fujimoto T , et al. Terminal restriction fragment length polymorphism analysis of the gut microbiota profiles of pediatric patients with inflammatory bowel disease. Digestion 2012; 86 (2) 129-135
  • 116 Schwiertz A, Jacobi M, Frick JS, Richter M, Rusch K, Köhler H. Microbiota in pediatric inflammatory bowel disease. J Pediatr 2010; 157 (2) 240-244 , e1
  • 117 Michail S, Durbin M, Turner D , et al. Alterations in the gut microbiome of children with severe ulcerative colitis. Inflamm Bowel Dis 2012; 18 (10) 1799-1808
  • 118 Conte MP, Schippa S, Zamboni I , et al. Gut-associated bacterial microbiota in paediatric patients with inflammatory bowel disease. Gut 2006; 55 (12) 1760-1767
  • 119 Negroni A, Costanzo M, Vitali R , et al. Characterization of adherent-invasive Escherichia coli isolated from pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis 2012; 18 (5) 913-924
  • 120 Bager P, Simonsen J, Nielsen NM, Frisch M. Cesarean section and offspring's risk of inflammatory bowel disease: a national cohort study. Inflamm Bowel Dis 2012; 18 (5) 857-862
  • 121 Decker E, Engelmann G, Findeisen A , et al. Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in children. Pediatrics 2010; 125 (6) e1433-e1440
  • 122 Klement E, Cohen RV, Boxman J, Joseph A, Reif S. Breastfeeding and risk of inflammatory bowel disease: a systematic review with meta-analysis. Am J Clin Nutr 2004; 80 (5) 1342-1352
  • 123 Barclay AR, Russell RK, Wilson ML, Gilmour WH, Satsangi J, Wilson DC. Systematic review: the role of breastfeeding in the development of pediatric inflammatory bowel disease. J Pediatr 2009; 155 (3) 421-426
  • 124 Kronman MP, Zaoutis TE, Haynes K, Feng R, Coffin SE. Antibiotic exposure and IBD development among children: a population-based cohort study. Pediatrics 2012; 130 (4) e794-e803
  • 125 Virta L, Auvinen A, Helenius H, Huovinen P, Kolho KL. Association of repeated exposure to antibiotics with the development of pediatric Crohn's disease—a nationwide, register-based Finnish case-control study. Am J Epidemiol 2012; 175 (8) 775-784
  • 126 Shaw SY, Blanchard JF, Bernstein CN. Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease. Am J Gastroenterol 2010; 105 (12) 2687-2692
  • 127 Hviid A, Svanström H, Frisch M. Antibiotic use and inflammatory bowel diseases in childhood. Gut 2011; 60 (1) 49-54
  • 128 Aujnarain A, Mack DR, Benchimol EI. The role of the environment in the development of pediatric inflammatory bowel disease. Curr Gastroenterol Rep 2013; 15 (6) 326-013
  • 129 Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology 2006; 130 (5) 1480-1491
  • 130 Saulnier DM, Riehle K, Mistretta TA , et al. Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology 2011; 141 (5) 1782-1791
  • 131 Rigsbee L, Agans R, Shankar V , et al. Quantitative profiling of gut microbiota of children with diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol 2012; 107 (11) 1740-1751
  • 132 Maxwell PR, Rink E, Kumar D, Mendall MA. Antibiotics increase functional abdominal symptoms. Am J Gastroenterol 2002; 97 (1) 104-108
  • 133 Ismail IH, Licciardi PV, Tang ML. Probiotic effects in allergic disease. J Paediatr Child Health 2013; 49 (9) 709-715
  • 134 Fiocchi A, Burks W, Bahna SL , et al; WAO Special Committee on Food Allergy and Nutrition. Clinical use of probiotics in pediatric allergy (CUPPA): A world allergy organization position paper. World Allergy Organ J 2012; 5 (11) 148-167
  • 135 Soh SE, Aw M, Gerez I , et al. Probiotic supplementation in the first 6 months of life in at risk Asian infants—effects on eczema and atopic sensitization at the age of 1 year. Clin Exp Allergy 2009; 39 (4) 571-578
  • 136 Taylor AL, Dunstan JA, Prescott SL. Probiotic supplementation for the first 6 months of life fails to reduce the risk of atopic dermatitis and increases the risk of allergen sensitization in high-risk children: a randomized controlled trial. J Allergy Clin Immunol 2007; 119 (1) 184-191
  • 137 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
  • 138 West CE, Hammarström ML, Hernell O. Probiotics during weaning reduce the incidence of eczema. Pediatr Allergy Immunol 2009; 20 (5) 430-437
  • 139 Weston S, Halbert A, Richmond P, Prescott SL. Effects of probiotics on atopic dermatitis: a randomised controlled trial. Arch Dis Child 2005; 90 (9) 892-897
  • 140 Woo SI, Kim JY, Lee YJ, Kim NS, Hahn YS. Effect of Lactobacillus sakei supplementation in children with atopic eczema-dermatitis syndrome. Ann Allergy Asthma Immunol 2010; 104 (4) 343-348
  • 141 Fölster-Holst R, Müller F, Schnopp N , et al. Prospective, randomized controlled trial on Lactobacillus rhamnosus in infants with moderate to severe atopic dermatitis. Br J Dermatol 2006; 155 (6) 1256-1261
  • 142 Osborn DA, Sinn JK. Prebiotics in infants for prevention of allergy. Cochrane Database Syst Rev 2013; 3: CD006474
  • 143 Gupta P, Andrew H, Kirschner BS, Guandalini S. Is lactobacillus GG helpful in children with Crohn's disease? Results of a preliminary, open-label study. J Pediatr Gastroenterol Nutr 2000; 31 (4) 453-457
  • 144 Bousvaros A, Guandalini S, Baldassano RN , et al. A randomized, double-blind trial of Lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn's disease. Inflamm Bowel Dis 2005; 11 (9) 833-839
  • 145 Prantera C, Scribano ML, Falasco G, Andreoli A, Luzi C. Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn's disease: a randomised controlled trial with Lactobacillus GG. Gut 2002; 51 (3) 405-409
  • 146 Rahimi R, Nikfar S, Rahimi F , et al. A meta-analysis on the efficacy of probiotics for maintenance of remission and prevention of clinical and endoscopic relapse in Crohn's disease. Dig Dis Sci 2008; 53 (9) 2524-2531
  • 147 Miele E, Pascarella F, Giannetti E, Quaglietta L, Baldassano RN, Staiano A. Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis. Am J Gastroenterol 2009; 104 (2) 437-443
  • 148 Huynh HQ, deBruyn J, Guan L , et al. Probiotic preparation VSL#3 induces remission in children with mild to moderate acute ulcerative colitis: a pilot study. Inflamm Bowel Dis 2009; 15 (5) 760-768
  • 149 Tursi A, Brandimarte G, Giorgetti GM, Forti G, Modeo ME, Gigliobianco A. Low-dose balsalazide plus a high-potency probiotic preparation is more effective than balsalazide alone or mesalazine in the treatment of acute mild-to-moderate ulcerative colitis. Med Sci Monit 2004; 10 (11) PI126-PI131
  • 150 Bibiloni R, Fedorak RN, Tannock GW , et al. VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis. Am J Gastroenterol 2005; 100 (7) 1539-1546
  • 151 Oliva S, Di Nardo G, Ferrari F , et al. Randomised clinical trial: the effectiveness of Lactobacillus reuteri ATCC 55730 rectal enema in children with active distal ulcerative colitis. Aliment Pharmacol Ther 2012; 35 (3) 327-334
  • 152 Floch MH, Walker WA, Madsen K , et al. Recommendations for probiotic use-2011 update. J Clin Gastroenterol 2011; 45 (Suppl): S168-S171
  • 153 Guandalini S. Update on the role of probiotics in the therapy of pediatric inflammatory bowel disease. Expert Rev Clin Immunol 2010; 6 (1) 47-54
  • 154 Welters CF, Heineman E, Thunnissen FB, van den Bogaard AE, Soeters PB, Baeten CG. Effect of dietary inulin supplementation on inflammation of pouch mucosa in patients with an ileal pouch-anal anastomosis. Dis Colon Rectum 2002; 45 (5) 621-627
  • 155 Mitsuyama K, Saiki T, Kanauchi O , et al. Treatment of ulcerative colitis with germinated barley foodstuff feeding: a pilot study. Aliment Pharmacol Ther 1998; 12 (12) 1225-1230
  • 156 Lindsay JO, Whelan K, Stagg AJ , et al. Clinical, microbiological, and immunological effects of fructo-oligosaccharide in patients with Crohn's disease. Gut 2006; 55 (3) 348-355
  • 157 Moayyedi P, Ford AC, Talley NJ , et al. The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut 2010; 59 (3) 325-332
  • 158 Whelan K. Probiotics and prebiotics in the management of irritable bowel syndrome: a review of recent clinical trials and systematic reviews. Curr Opin Clin Nutr Metab Care 2011; 14 (6) 581-587
  • 159 Huertas-Ceballos AA, Logan S, Bennett C, Macarthur C. Dietary interventions for recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in childhood. Cochrane Database Syst Rev 2009; (1) CD003019
  • 160 Francavilla R, Miniello V, Magistà AM , et al. A randomized controlled trial of Lactobacillus GG in children with functional abdominal pain. Pediatrics 2010; 126 (6) e1445-e1452
  • 161 Guandalini S, Magazzù G, Chiaro A , et al. VSL#3 improves symptoms in children with irritable bowel syndrome: a multicenter, randomized, placebo-controlled, double-blind, crossover study. J Pediatr Gastroenterol Nutr 2010; 51 (1) 24-30
  • 162 Staudacher HM, Whelan K, Irving PM, Lomer MC. Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) versus standard dietary advice in patients with irritable bowel syndrome. J Hum Nutr Diet 2011; 24 (5) 487-495
  • 163 Alfaleh K, Anabrees J, Bassler D, Al-Kharfi T. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2011; (3) CD005496
  • 164 Downard CD, Renaud E, St Peter SD , et al; 2012 American Pediatric Surgical Association Outcomes Clinical Trials Committee. Treatment of necrotizing enterocolitis: An American pediatric surgical association outcomes and clinical trials committee systematic review. J Pediatr Surg 2012; 47 (11) 2111-2122
  • 165 Fallon EM, Nehra D, Potemkin AK , et al; American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors. A.S.P.E.N. clinical guidelines: nutrition support of neonatal patients at risk for necrotizing enterocolitis. JPEN J Parenter Enteral Nutr 2012; 36 (5) 506-523
  • 166 Lee JH. An update on necrotizing enterocolitis: pathogenesis and preventive strategies. Korean J Pediatr 2011; 54 (9) 368-372
  • 167 Vandenplas Y, De Greef E, Devreker T, Veereman-Wauters G, Hauser B. Probiotics and prebiotics in infants and children. Curr Infect Dis Rep 2013; 15 (3) 251-262
  • 168 Chapkin RS, Zhao C, Ivanov I , et al. Noninvasive stool-based detection of infant gastrointestinal development using gene expression profiles from exfoliated epithelial cells. Am J Physiol Gastrointest Liver Physiol 2010; 298 (5) G582-G589
  • 169 Schwartz S, Friedberg I, Ivanov IV , et al. A metagenomic study of diet-dependent interaction between gut microbiota and host in infants reveals differences in immune response. Genome Biol 2012; 13 (4) r32-r2012