Neonatology pp 503-534 | Cite as

Physiology of the Gastrointestinal Tract in Newborns

  • Arieh RiskinEmail author
  • Carlo Agostoni
  • Raanan Shamir
Reference work entry


The chapter will discuss the different elements of the developmental physiology of the gastrointestinal tract, including organogenesis, vascularization, neural control, and host defense mechanisms. The development of gastrointestinal motility and of the digestive and absorptive functions and how they relate to feeding and nutrition of the preterm and term neonates will be outlined. Aspects of morphology, physiology, and biochemistry of the developing gastrointestinal tract as well as more recent findings at the molecular biology level will be discussed. Application of this basic knowledge on intestinal functional development should be used in order to improve nutrition for preterm infants and prevent short- and long-term morbidities that may be related to inadequate or poor feeding and nutrition:
  1. (A)

    Development of the gastrointestinal tract – organogenesis and function

  2. (B)


  3. (C)

    Neural control of motor function and gastrointestinal motility

  4. (D)

    Digestion and absorption

  5. (E)

    Host defense

  6. (F)

    Gastrointestinal hormones and peptides (These are discussed in  Chap. 35, “Hormones and Gastrointestinal Function of Newborns”)



  1. Agostoni C, Carratu B, Boniglia C, Lammardo AM, Riva E, Sanzini E (2000) Free glutamine and glutamic acid increase in human milk through a three-month lactation period. J Pediatr Gastroenterol Nutr 31(5):508–512CrossRefPubMedGoogle Scholar
  2. Agostoni C, Axelsson I, Braegger C, Goulet O, Koletzko B, Michaelsen KF et al (2004a) Probiotic bacteria in dietetic products for infants: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 38(4):365–374CrossRefPubMedGoogle Scholar
  3. Agostoni C, Axelsson I, Goulet O, Koletzko B, Michaelsen KF, Puntis JW et al (2004b) Prebiotic oligosaccharides in dietetic products for infants: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 39(5):465–473CrossRefPubMedGoogle Scholar
  4. AlFaleh K, Anabrees J (2014a) Probiotics for prevention of necrotizing enterocolitis in preterm infants. Evid Based Child Health: Cochrane Rev J 9(3):584–671CrossRefGoogle Scholar
  5. AlFaleh K, Anabrees J (2014b) Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 4:CD005496Google Scholar
  6. Al-Tawil Y, Klee G, Berseth CL (2002) Extrinsic neural regulation of antroduodenal motor activity in preterm infants. Dig Dis Sci 47(12):2657–2663CrossRefPubMedGoogle Scholar
  7. Altschuler SM, Bao XM, Bieger D, Hopkins DA, Miselis RR (1989) Viscerotopic representation of the upper alimentary tract in the rat: sensory ganglia and nuclei of the solitary and spinal trigeminal tracts. J Comp Neurol 283(2):248–268CrossRefPubMedGoogle Scholar
  8. Anderson RB, Newgreen DF, Young HM (2006) Neural crest and the development of the enteric nervous system. Adv Exp Med Biol 589:181–196CrossRefPubMedGoogle Scholar
  9. Baetge G, Pintar JE, Gershon MD (1990) Transiently catecholaminergic (TC) cells in the bowel of the fetal rat: precursors of noncatecholaminergic enteric neurons. Dev Biol 141(2):353–380CrossRefPubMedGoogle Scholar
  10. Bar A, Riskin A, Iancu T, Manov I, Arad A, Shaoul R (2007) A newborn infant with protracted diarrhea and metabolic acidosis. J Pediatr 150(2):198–201CrossRefPubMedGoogle Scholar
  11. Beck F (2002) Homeobox genes in gut development. Gut 51(3):450–454PubMedCentralCrossRefPubMedGoogle Scholar
  12. Becker RM, Wu G, Galanko JA, Chen W, Maynor AR, Bose CL et al (2000) Reduced serum amino acid concentrations in infants with necrotizing enterocolitis. J Pediatr 137(6):785–793CrossRefPubMedGoogle Scholar
  13. Beck-Sague CM, Azimi P, Fonseca SN, Baltimore RS, Powell DA, Bland LA et al (1994) Bloodstream infections in neonatal intensive care unit patients: results of a multicenter study. Pediatr Infect Dis J 13(12):1110–1116CrossRefPubMedGoogle Scholar
  14. Berseth CL (1989) Gestational evolution of small intestine motility in preterm and term infants. J Pediatr 115:646–651CrossRefPubMedGoogle Scholar
  15. Berseth CL (1992) Effect of early feeding on maturation of the preterm infant’s small intestine. J Pediatr 120(6):947–953CrossRefPubMedGoogle Scholar
  16. Berseth CL (1996) Gastrointestinal motility in the neonate. Clin Perinatol 23(2):179–190CrossRefPubMedGoogle Scholar
  17. Berseth CL (2005) Developmental anatomy and physiology of the gastrointestinal tract. In: Taeusch HW, Ballard RA (eds) Avery’s diseases of the newborn, 8th edn. W.B. Saunders Company, PhiladelphiaGoogle Scholar
  18. Berthoud HR, Jedrzejewska A, Powley TL (1990) Simultaneous labeling of vagal innervation of the gut and afferent projections from the visceral forebrain with dil injected into the dorsal vagal complex in the rat. J Comp Neurol 301(1):65–79CrossRefPubMedGoogle Scholar
  19. Bin-Nun A, Bromiker R, Wilschanski M, Kaplan M, Rudensky B, Caplan M et al (2005) Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr 147(2):192–196CrossRefPubMedGoogle Scholar
  20. Bohles H (1997) Antioxidative vitamins in prematurely and maturely born infants. Int J Vitam Nutr Res 67(5):321–328PubMedGoogle Scholar
  21. Bosscher D, Van Caillie-Bertrand M, Robberecht H, Van DK, Van CR, Deelstra H (2001) In vitro availability of calcium, iron, and zinc from first-age infant formulae and human milk. J Pediatr Gastroenterol Nutr 32(1):54–58CrossRefPubMedGoogle Scholar
  22. Bracco U (1994) Effect of triglyceride structure on fat absorption. Am J Clin Nutr 60(6 Suppl):1002S–1009SCrossRefPubMedGoogle Scholar
  23. Caicedo RA, Schanler RJ, Li N, Neu J (2005) The developing intestinal ecosystem: implications for the neonate. Pediatr Res 58(4):625–628CrossRefPubMedGoogle Scholar
  24. Calder PC, Krauss-Etschmann S, de Jong EC, Dupont C, Frick JS, Frokiaer H et al (2006) Early nutrition and immunity – progress and perspectives. Br J Nutr 96(4):774–790PubMedGoogle Scholar
  25. Caplan MS, Jilling T (2001) The role of polyunsaturated fatty acid supplementation in intestinal inflammation and neonatal necrotizing enterocolitis. Lipids 36(9):1053–1057CrossRefPubMedGoogle Scholar
  26. Chirico G, Marzollo R, Cortinovis S, Fonte C, Gasparoni A (2008) Antiinfective properties of human milk. J Nutr 138(9):1801S–1806SCrossRefPubMedGoogle Scholar
  27. Chowanadisai W, Lonnerdal B (2002) Alpha(1)-antitrypsin and antichymotrypsin in human milk: origin, concentrations, and stability. Am J Clin Nutr 76(4):828–833CrossRefPubMedGoogle Scholar
  28. Dani C, Biadaioli R, Bertini G, Martelli E, Rubaltelli FF (2002) Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study. Biol Neonate 82(2):103–108CrossRefPubMedGoogle Scholar
  29. Davidson NO, Hausman AM, Ifkovits CA, Buse JB, Gould GW, Burant CF et al (1992) Human intestinal glucose transporter expression and localization of GLUT5. Am J Physiol 262(3 Pt 1):C795–C800CrossRefPubMedGoogle Scholar
  30. Davis MJ, Hill MA (1999) Signaling mechanisms underlying the vascular myogenic response. Physiol Rev 79(2):387–423CrossRefPubMedGoogle Scholar
  31. de Lorijn LF, Voskuijl WP, Omari TI, Kok JH, Taminiau JA, Benninga MA (2005) Assessment of the rectoanal inhibitory reflex in preterm infants with delayed meconium passage. J Pediatr Gastroenterol Nutr 40(4):434–437CrossRefPubMedGoogle Scholar
  32. de Santa BP, van den Brink GR, Roberts DJ (2003) Development and differentiation of the intestinal epithelium. Cell Mol Life Sci 60(7):1322–1332CrossRefGoogle Scholar
  33. DeMarco V, Dyess K, Strauss D, West CM, Neu J (1999) Inhibition of glutamine synthetase decreases proliferation of cultured rat intestinal epithelial cells. J Nutr 129(1):57–62CrossRefPubMedGoogle Scholar
  34. Deshpande G, Rao S, Patole S, Bulsara M (2010) Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics 125(5):921–930CrossRefPubMedGoogle Scholar
  35. Deshpande GC, Rao SC, Keil AD, Patole SK (2011) Evidence-based guidelines for use of probiotics in preterm neonates. BMC Med 9:92PubMedCentralCrossRefPubMedGoogle Scholar
  36. Di Mauro A, Neu J, Riezzo G, Raimondi F, Martinelli D, Francavilla R et al (2013) Gastrointestinal function development and microbiota. Ital J Pediatr 39:15PubMedCentralCrossRefPubMedGoogle Scholar
  37. Di LC, Flores AF, Hyman PE (1995) Age-related changes in colon motility. J Pediatr 127(4):593–596CrossRefGoogle Scholar
  38. Faure C, Chalazonitis A, Rheaume C, Bouchard G, Sampathkumar SG, Yarema KJ et al (2007) Gangliogenesis in the enteric nervous system: roles of the polysialylation of the neural cell adhesion molecule and its regulation by bone morphogenetic protein-4. Dev Dyn 236(1):44–59CrossRefPubMedGoogle Scholar
  39. Fekete E, Benedeczky I, Timmermans JP, Resch BA, Scheuermann DW (1996) Sequential pattern of nerve-muscle contacts in the small intestine of developing human fetus. An ultrastructural and immunohistochemical study. Histol Histopathol 11(4):845–850PubMedGoogle Scholar
  40. Furness JB, Costa M (1987) Arrangement of the enteric plexuses. In: Furness JB, Costa M (eds) The enteric nervous system. Churchill Livingstone, New YorkGoogle Scholar
  41. Fusunyan RD, Nanthakumar NN, Baldeon ME, Walker WA (2001) Evidence for an innate immune response in the immature human intestine: toll-like receptors on fetal enterocytes. Pediatr Res 49(4):589–593CrossRefPubMedGoogle Scholar
  42. Gardner CE Jr, Hart D (1934) Arch Surg 29:942CrossRefGoogle Scholar
  43. Garofalo RP, Goldman AS (1999) Expression of functional immunomodulatory and anti-inflammatory factors in human milk. Clin Perinatol 26(2):361–377CrossRefPubMedGoogle Scholar
  44. Gaynes RP, Edwards JR, Jarvis WR, Culver DH, Tolson JS, Martone WJ (1996) Nosocomial infections among neonates in high-risk nurseries in the United States. National Nosocomial Infections Surveillance System. Pediatrics 98(3 Pt 1):357–361PubMedGoogle Scholar
  45. Gershon MD, Chalazonitis A, Rothman TP (1993) From neural crest to bowel: development of the enteric nervous system. J Neurobiol 24(2):199–214CrossRefPubMedGoogle Scholar
  46. Gewolb IH, Schwalbe RS, Taciak VL, Harrison TS, Panigrahi P (1999) Stool microflora in extremely low birthweight infants. Arch Dis Child Fetal Neonatal Ed 80(3):F167–F173PubMedCentralCrossRefPubMedGoogle Scholar
  47. Gewolb IH, Vice FL, Schwietzer-Kenney EL, Taciak VL, Bosma JF (2001) Developmental patterns of rhythmic suck and swallow in preterm infants. Dev Med Child Neurol 43(1):22–27CrossRefPubMedGoogle Scholar
  48. Gork AS, Ehrenkranz RA, Bracken MB (2008) Continuous infusion versus intermittent bolus doses of indomethacin for patent ductus arteriosus closure in symptomatic preterm infants. Cochrane Database Syst Rev 1:CD006071Google Scholar
  49. Greer FR (2000) Vitamin metabolism and requirements in the micropremie. Clin Perinatol 27(1):95–118, viCrossRefPubMedGoogle Scholar
  50. Greer FR (2001) Do breastfed infants need supplemental vitamins? Pediatr Clin North Am 48(2):415–423CrossRefPubMedGoogle Scholar
  51. Grider JR, Murthy KS (2008) Autoinhibition of endothelial nitric oxide synthase (eNOS) in gut smooth muscle by nitric oxide. Regul Pept 151(1–3):75–79PubMedCentralCrossRefPubMedGoogle Scholar
  52. Guarner F, Malagelada JR (2003) Gut flora in health and disease. Lancet 361(9356):512–519CrossRefPubMedGoogle Scholar
  53. Gupta A, Gulati P, Kim W, Fernandez S, Shaker R, Jadcherla SR (2009) Effect of postnatal maturation on the mechanisms of esophageal propulsion in preterm human neonates: primary and secondary peristalsis. Am J Gastroenterol 104(2):411–419PubMedCentralCrossRefPubMedGoogle Scholar
  54. Halsted CH (2003) Absorption of water-soluble vitamins. Curr Opin Gastroenterol 19(2):113–117CrossRefPubMedGoogle Scholar
  55. Hamosh M (1987) Lipid metabolism in premature infants. Biol Neonate 52(Suppl 1):50–64CrossRefPubMedGoogle Scholar
  56. Hamosh M (1990) Lingual and gastric lipases. Nutrition 6(6):421–428PubMedGoogle Scholar
  57. Hamosh M (1995) Lipid metabolism in pediatric nutrition. Pediatr Clin North Am 42(4):839–859CrossRefPubMedGoogle Scholar
  58. Harvey BJ, Alzamora R, Stubbs AK, Irnaten M, McEneaney V, Thomas W (2008) Rapid responses to aldosterone in the kidney and colon. J Steroid Biochem Mol Biol 108(3–5):310–317CrossRefPubMedGoogle Scholar
  59. Havranek T, Thompson Z, Carver JD (2006) Factors that influence mesenteric artery blood flow velocity in newborn preterm infants. J Perinatol 26(8):493–497CrossRefPubMedGoogle Scholar
  60. Hecht G (1999) Innate mechanisms of epithelial host defense: spotlight on intestine. Am J Physiol 277(3 Pt 1):C351–C358CrossRefPubMedGoogle Scholar
  61. Heird WC, Lapillonne A (2005) The role of essential fatty acids in development. Annu Rev Nutr 25:549–571CrossRefPubMedGoogle Scholar
  62. Henderson TR, Hamosh M, Armand M, Mehta NR, Hamosh P (2001) Gastric proteolysis in preterm infants fed mother’s milk or formula. Adv Exp Med Biol 501:403–408CrossRefPubMedGoogle Scholar
  63. Hernell O, Blackberg L (1994) Human milk bile salt-stimulated lipase: functional and molecular aspects. J Pediatr 125(5 Pt 2):S56–S61CrossRefPubMedGoogle Scholar
  64. Hoecker C, Nelle M, Poeschl J, Beedgen B, Linderkamp O (2002) Caffeine impairs cerebral and intestinal blood flow velocity in preterm infants. Pediatrics 109(5):784–787CrossRefPubMedGoogle Scholar
  65. Holle GE, Forth W (1990) Myoelectric activity of small intestine after chemical ablation of myenteric neurons. Am J Physiol 258(4 Pt 1):G519–G526PubMedGoogle Scholar
  66. Hooper LV, Midtvedt T, Gordon JI (2002) How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annu Rev Nutr 22:283–307CrossRefPubMedGoogle Scholar
  67. Houghton LA, Vieth R (2006) The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr 84(4):694–697CrossRefPubMedGoogle Scholar
  68. Hoyos AB (1999) Reduced incidence of necrotizing enterocolitis associated with enteral administration of Lactobacillus acidophilus and Bifidobacterium infantis to neonates in an intensive care unit. Int J Infect Dis 3(4):197–202CrossRefPubMedGoogle Scholar
  69. Huizinga JD, Thuneberg L, Kluppel M, Malysz J, Mikkelsen HB, Bernstein A (1995) W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 373(6512):347–349CrossRefPubMedGoogle Scholar
  70. Huizinga JD, Ambrous K, Der-Silaphet T (1998) Co-operation between neural and myogenic mechanisms in the control of distension-induced peristalsis in the mouse small intestine. J Physiol 506(Pt 3):843–856PubMedCentralCrossRefPubMedGoogle Scholar
  71. Iqbal J, Hussain M (2009) Intestinal lipid absorption. Am J Physiol Endocrinol Metab 296:E1183PubMedCentralCrossRefPubMedGoogle Scholar
  72. Isolauri E (2001) Probiotics in human disease. Am J Clin Nutr 73(6):1142S–1146SCrossRefPubMedGoogle Scholar
  73. Ittmann PI, Amarnath R, Berseth CL (1992) Maturation of antroduodenal motor activity in preterm and term infants. Dig Dis Sci 37(1):14–19CrossRefPubMedGoogle Scholar
  74. Kawai T, Fushiki T (2003) Importance of lipolysis in oral cavity for orosensory detection of fat. Am J Physiol Regul Integr Comp Physiol 285(2):R447–R454CrossRefPubMedGoogle Scholar
  75. Keller KM, Wirth S, Baumann W, Sule D, Booth IW (1990) Defective jejunal brush border membrane sodium/proton exchange in association with lethal familial protracted diarrhoea. Gut 31(10):1156–1158PubMedCentralCrossRefPubMedGoogle Scholar
  76. Kelly EJ, Lagopoulos M, Primrose JN (1993a) Immunocytochemical localisation of parietal cells and G cells in the developing human stomach. Gut 34(8):1057–1059PubMedCentralCrossRefPubMedGoogle Scholar
  77. Kelly EJ, Newell SJ, Brownlee KG, Primrose JN, Dear PR (1993b) Gastric acid secretion in preterm infants. Early Hum Dev 35(3):215–220CrossRefPubMedGoogle Scholar
  78. Kelly EJ, Newell SJ, Brownlee KG, Farmery SM, Cullinane C, Reid WA et al (1997) Role of epidermal growth factor and transforming growth factor alpha in the developing stomach. Arch Dis Child Fetal Neonatal Ed 76(3):F158–F162PubMedCentralCrossRefPubMedGoogle Scholar
  79. Kennedy K, Fewtrell MS, Morley R, Abbott R, Quinlan PT, Wells JC et al (1999) Double-blind, randomized trial of a synthetic triacylglycerol in formula-fed term infants: effects on stool biochemistry, stool characteristics, and bone mineralization. Am J Clin Nutr 70(5):920–927CrossRefPubMedGoogle Scholar
  80. Kere J, Lohi H, Hoglund P (1999) Genetic disorders of membrane transport III. Congenital chloride diarrhea. Am J Physiol 276(1 Pt 1):G7–G13PubMedGoogle Scholar
  81. Kessler JP (1993) Involvement of excitatory amino acids in the activity of swallowing-related neurons of the ventro-lateral medulla. Brain Res 603(2):353–357CrossRefPubMedGoogle Scholar
  82. Kien CL, Heitlinger LA, Li BU, Murray RD (1989) Digestion, absorption, and fermentation of carbohydrates. Semin Perinatol 13(2):78–87PubMedGoogle Scholar
  83. Kirchgessner AL, Gershon MD (1989) Identification of vagal efferent fibers and putative target neurons in the enteric nervous system of the rat. J Comp Neurol 285(1):38–53CrossRefPubMedGoogle Scholar
  84. Kitajima H, Sumida Y, Tanaka R, Yuki N, Takayama H, Fujimura M (1997) Early administration of Bifidobacterium breve to preterm infants: randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 76(2):F101–F107PubMedCentralCrossRefPubMedGoogle Scholar
  85. Knol J, Boehm G, Lidestri M, Negretti F, Jelinek J, Agosti M et al (2005) Increase of faecal bifidobacteria due to dietary oligosaccharides induces a reduction of clinically relevant pathogen germs in the faeces of formula-fed preterm infants. Acta Paediatr Suppl 94(449):31–33CrossRefPubMedGoogle Scholar
  86. Koenig WJ, Amarnath RP, Hench V, Berseth CL (1995) Manometrics for preterm and term infants: a new tool for old questions. Pediatrics 95(2):203–206PubMedGoogle Scholar
  87. Kolacek S, Puntis JW, Lloyd DR, Brown GA, Booth IW (1990) Ontogeny of pancreatic exocrine function. Arch Dis Child 65(2):178–181PubMedCentralCrossRefPubMedGoogle Scholar
  88. Koletzko B, Demmelmair H, Socha P (1998) Nutritional support of infants and children: supply and metabolism of lipids. Baillieres Clin Gastroenterol 12(4):671–696CrossRefPubMedGoogle Scholar
  89. Koletzko S, Jesch I, Faus-Kebetaler T, Briner J, Meier-Ruge W, Muntefering H et al (1999) Rectal biopsy for diagnosis of intestinal neuronal dysplasia in children: a prospective multicentre study on interobserver variation and clinical outcome. Gut 44(6):853–861PubMedCentralCrossRefPubMedGoogle Scholar
  90. Land MH, Rouster-Stevens K, Woods CR, Cannon ML, Cnota J, Shetty AK (2005) Lactobacillus sepsis associated with probiotic therapy. Pediatrics 115(1):178–181CrossRefPubMedGoogle Scholar
  91. Lau C, Alagugurusamy R, Schanler RJ, Smith EO, Shulman RJ (2000) Characterization of the developmental stages of sucking in preterm infants during bottle feeding. Acta Paediatr 89(7):846–852CrossRefPubMedGoogle Scholar
  92. Lau C, Smith EO, Schanler RJ (2003) Coordination of suck-swallow and swallow respiration in preterm infants. Acta Paediatr 92(6):721–727CrossRefPubMedGoogle Scholar
  93. Lecoin L, Gabella G, Le DN (1996) Origin of the c-kit-positive interstitial cells in the avian bowel. Development 122(3):725–733PubMedGoogle Scholar
  94. Li N, Neu J (2009) Glutamine deprivation alters intestinal tight junctions via a PI3-K/Akt mediated pathway in Caco-2 cells. J Nutr 139(4):710–714PubMedCentralCrossRefPubMedGoogle Scholar
  95. Lichnovsky V, Lojda Z (1992) Early prenatal development of the brush border enzymes in the embryonal intestine. Acta Univ Palacki Olomuc Fac Med 134:27–31PubMedGoogle Scholar
  96. Lidestri M, Agosti M, Marini A, Boehm G (2003) Oligosaccharides might stimulate calcium absorption in formula-fed preterm infants. Acta Paediatr Suppl 91(441):91–92PubMedGoogle Scholar
  97. Lin HC, Su BH, Chen AC, Lin TW, Tsai CH, Yeh TF et al (2005) Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. Pediatrics 115(1):1–4CrossRefPubMedGoogle Scholar
  98. Lin HC, Hsu CH, Chen HL, Chung MY, Hsu JF, Lien RI et al (2008) Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial. Pediatrics 122(4):693–700CrossRefPubMedGoogle Scholar
  99. Lindberg T, Skude G (1982) Amylase in human milk. Pediatrics 70(2):235–238PubMedGoogle Scholar
  100. Lohi H, Kujala M, Makela S, Lehtonen E, Kestila M, Saarialho-Kere U et al (2002) Functional characterization of three novel tissue-specific anion exchangers SLC26A7, -A8, and -A9. J Biol Chem 277(16):14246–14254CrossRefPubMedGoogle Scholar
  101. Lopez-Alonso M, Moya MJ, Cabo JA, Ribas J, del Carmen MM, Silny J et al (2006) Twenty-four-hour esophageal impedance-pH monitoring in healthy preterm neonates: rate and characteristics of acid, weakly acidic, and weakly alkaline gastroesophageal reflux. Pediatrics 118(2):e299–e308CrossRefPubMedGoogle Scholar
  102. Louis NA, Lin PW (2009) The intestinal immune barrier. NeoReviews 10(4):e180–e190CrossRefGoogle Scholar
  103. Louis NA, Hamilton KE, Canny G, Shekels LL, Ho SB, Colgan SP (2006) Selective induction of mucin-3 by hypoxia in intestinal epithelia. J Cell Biochem 99(6):1616–1627CrossRefPubMedGoogle Scholar
  104. Lu J, Jilling T, Li D, Caplan MS (2007) Polyunsaturated fatty acid supplementation alters proinflammatory gene expression and reduces the incidence of necrotizing enterocolitis in a neonatal rat model. Pediatr Res 61(4):427–432PubMedCentralCrossRefPubMedGoogle Scholar
  105. Malo C (1990) Separation of two distinct Na+/d-glucose cotransport systems in the human fetal jejunum by means of their differential specificity for 3-O-methylglucose. Biochim Biophys Acta 1022(1):8–16CrossRefPubMedGoogle Scholar
  106. Malo C, Berteloot A (1991) Analysis of kinetic data in transport studies: new insights from kinetic studies of Na(+)-d-glucose cotransport in human intestinal brush-border membrane vesicles using a fast sampling, rapid filtration apparatus. J Membr Biol 122(2):127–141CrossRefPubMedGoogle Scholar
  107. Martinussen M, Brubakk AM, Vik T, Yao AC (1996) Mesenteric blood flow velocity and its relation to transitional circulatory adaptation in appropriate for gestational age preterm infants. Pediatr Res 39(2):275–280CrossRefPubMedGoogle Scholar
  108. Medzhitov R (2007) Recognition of microorganisms and activation of the immune response. Nature 449(7164):819–826CrossRefPubMedGoogle Scholar
  109. Menard D, Dagenais P, Calvert R (1994) Morphological changes and cellular proliferation in mouse colon during fetal and postnatal development. Anat Rec 238(3):349–359CrossRefPubMedGoogle Scholar
  110. Mihatsch WA, Hoegel J, Pohlandt F (2006) Prebiotic oligosaccharides reduce stool viscosity and accelerate gastrointestinal transport in preterm infants. Acta Paediatr 95(7):843–848CrossRefPubMedGoogle Scholar
  111. Mihatsch WA, Braegger CP, Decsi T, Kolacek S, Lanzinger H, Mayer B et al (2012) Critical systematic review of the level of evidence for routine use of probiotics for reduction of mortality and prevention of necrotizing enterocolitis and sepsis in preterm infants. Clin Nutr 31:6–15CrossRefPubMedGoogle Scholar
  112. Miller H, Zhang J, Kuolee R, Patel GB, Chen W (2007) Intestinal M cells: the fallible sentinels? World J Gastroenterol 13(10):1477–1486PubMedCentralCrossRefPubMedGoogle Scholar
  113. Mimouni FB, Shamir R (2009) Vitamin D requirements in the first year of life. Curr Opin Clin Nutr Metab Care 12(3):287–292CrossRefPubMedGoogle Scholar
  114. Montgomery RK, Mulberg AE, Grand RJ (1999) Development of the human gastrointestinal tract: twenty years of progress. Gastroenterology 116(3):702–731CrossRefPubMedGoogle Scholar
  115. Moro G, Minoli I, Mosca M, Fanaro S, Jelinek J, Stahl B et al (2002) Dosage-related bifidogenic effects of galacto- and fructooligosaccharides in formula-fed term infants. J Pediatr Gastroenterol Nutr 34(3):291–295CrossRefPubMedGoogle Scholar
  116. Mouterde O, Dacher JN, Basuyau JP, Mallet E (1992) Gastric secretion in infants. Application to the study of sudden infant death syndrome and apparently life-threatening events. Biol Neonate 62(1):15–22CrossRefPubMedGoogle Scholar
  117. Murch SH, Winyard PJ, Koletzko S, Wehner B, Cheema HA, Risdon RA et al (1996) Congenital enterocyte heparan sulphate deficiency with massive albumin loss, secretory diarrhoea, and malnutrition. Lancet 347(9011):1299–1301CrossRefPubMedGoogle Scholar
  118. Murray RD, Boutton TW, Klein PD, Gilbert M, Paule CL, MacLean WC Jr (1990) Comparative absorption of [13C]glucose and [13C]lactose by premature infants. Am J Clin Nutr 51(1):59–66CrossRefPubMedGoogle Scholar
  119. Nankervis CA, Nowicki PT (2000) Role of endothelin-1 in regulation of the postnatal intestinal circulation. Am J Physiol Gastrointest Liver Physiol 278(3):G367–G375CrossRefPubMedGoogle Scholar
  120. Nanthakumar NN, Fusunyan RD, Sanderson I, Walker WA (2000) Inflammation in the developing human intestine: a possible pathophysiologic contribution to necrotizing enterocolitis. Proc Natl Acad Sci U S A 97(11):6043–6048PubMedCentralCrossRefPubMedGoogle Scholar
  121. Neish AS (2009) Microbes in gastrointestinal health and disease. Gastroenterology 136(1):65–80CrossRefPubMedGoogle Scholar
  122. Neu J, Caicedo R (2005) Probiotics: protecting the intestinal ecosystem? J Pediatr 147(2):143–146CrossRefPubMedGoogle Scholar
  123. Neu J, Roig JC, Meetze WH, Veerman M, Carter C, Millsaps M et al (1997) Enteral glutamine supplementation for very low birth weight infants decreases morbidity. J Pediatr 131(5):691–699CrossRefPubMedGoogle Scholar
  124. Newell SJ, Sarkar PK, Durbin GM, Booth IW, McNeish AS (1988) Maturation of the lower oesophageal sphincter in the preterm baby. Gut 29(2):167–172PubMedCentralCrossRefPubMedGoogle Scholar
  125. Newgreen D, Young HM (2002a) Enteric nervous system: development and developmental disturbances – part 1. Pediatr Dev Pathol 5(3):224–247PubMedGoogle Scholar
  126. Newgreen D, Young HM (2002b) Enteric nervous system: development and developmental disturbances – part 2. Pediatr Dev Pathol 5(4):329–349CrossRefPubMedGoogle Scholar
  127. Niot I, Poirier H, Tran TT, Besnard P (2009) Intestinal absorption of long-chain fatty acids: evidence and uncertainties. Prog Lipid Res 48(2):101–115CrossRefPubMedGoogle Scholar
  128. Nowicki PT (1998) Postnatal changes in gut hemodynamics: a possible role for substance P. Am J Physiol 274(6 Pt 1):G1142–G1150PubMedGoogle Scholar
  129. Nurko S (2005) What’s the value of diagnostic tools in defecation disorders? J Pediatr Gastroenterol Nutr 41(Suppl 1):S53–S55CrossRefPubMedGoogle Scholar
  130. Nusrat A, Turner JR, Madara JL (2000) Molecular physiology and pathophysiology of tight junctions. IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells. Am J Physiol Gastrointest Liver Physiol 279(5):G851–G857CrossRefPubMedGoogle Scholar
  131. Omari TI, Benninga MA, Barnett CP, Haslam RR, Davidson GP, Dent J (1999) Characterization of esophageal body and lower esophageal sphincter motor function in the very premature neonate. J Pediatr 135(4):517–521CrossRefPubMedGoogle Scholar
  132. Park CW, Moon KC, Park JS, Jun JK, Romero R, Yoon BH (2009) The involvement of human amnion in histologic chorioamnionitis is an indicator that a fetal and an intra-amniotic inflammatory response is more likely and severe: clinical implications. Placenta 30(1):56–61CrossRefPubMedGoogle Scholar
  133. Phillips SF (1997) The growth of knowledge in human digestion and absorption. Gastroenterology 112(4):1404–1405CrossRefPubMedGoogle Scholar
  134. Pickering LK, Granoff DM, Erickson JR, Masor ML, Cordle CT, Schaller JP et al (1998) Modulation of the immune system by human milk and infant formula containing nucleotides. Pediatrics 101(2):242–249CrossRefPubMedGoogle Scholar
  135. Pinto D, Clevers H (2005) Wnt control of stem cells and differentiation in the intestinal epithelium. Exp Cell Res 306(2):357–363CrossRefPubMedGoogle Scholar
  136. Potsic B, Holliday N, Lewis P, Samuelson D, DeMarco V, Neu J (2002) Glutamine supplementation and deprivation: effect on artificially reared rat small intestinal morphology. Pediatr Res 52(3):430–436CrossRefPubMedGoogle Scholar
  137. Ramirez M, Amate L, Gil A (2001) Absorption and distribution of dietary fatty acids from different sources. Early Hum Dev 65(Suppl):S95–S101CrossRefPubMedGoogle Scholar
  138. Ramirez A, Wong WW, Shulman RJ (2006) Factors regulating gastric emptying in preterm infants. J Pediatr 149(4):475–479CrossRefPubMedGoogle Scholar
  139. Rao SS, Welcher K (1996) Periodic rectal motor activity: the intrinsic colonic gatekeeper? Am J Gastroenterol 91(5):890–897PubMedGoogle Scholar
  140. Reber KM, Nankervis CA, Nowicki PT (2002) Newborn intestinal circulation. Physiology and pathophysiology. Clin Perinatol 29(1):23–39CrossRefPubMedGoogle Scholar
  141. Riskin A, Hochwald O, Bader D, Srugo I, Gabi N, Kugelman A et al (2010) The effects of lactulose supplementation to enteral feedings in premature infants: a pilot study. J Pediatr 156(2):209–214CrossRefPubMedGoogle Scholar
  142. Salminen S, Isolauri E (2006) Intestinal colonization, microbiota, and probiotics. J Pediatr 149:S115–S120CrossRefGoogle Scholar
  143. Salzman NH, Underwood MA, Bevins CL (2007) Paneth cells, defensins, and the commensal microbiota: a hypothesis on intimate interplay at the intestinal mucosa. Semin Immunol 19(2):70–83CrossRefPubMedGoogle Scholar
  144. Sarna SK, Otterson MF (1988) Gastrointestinal motility: some basic concepts. Pharmacology 36(Suppl 1):7–14CrossRefPubMedGoogle Scholar
  145. Sarna SK, Otterson MF (1989) Small intestinal physiology and pathophysiology. Gastroenterol Clin North Am 18(2):375–404PubMedGoogle Scholar
  146. Saur D, Vanderwinden JM, Seidler B, Schmid RM, De Laet MH, Allescher HD (2004) Single-nucleotide promoter polymorphism alters transcription of neuronal nitric oxide synthase exon 1c in infantile hypertrophic pyloric stenosis. Proc Natl Acad Sci U S A 101(6):1662–1667PubMedCentralCrossRefPubMedGoogle Scholar
  147. Schanler RJ (1995) Suitability of human milk for the low-birthweight infant. Clin Perinatol 22(1):207–222CrossRefPubMedGoogle Scholar
  148. Schanler RJ, Rifka M (1994) Calcium, phosphorus and magnesium needs for the low-birth-weight infant. Acta Paediatr Suppl 405:111–116CrossRefPubMedGoogle Scholar
  149. Schultz SG (2007) From a pump handle to oral rehydration therapy: a model of translational research. Adv Physiol Educ 31(4):288–293CrossRefPubMedGoogle Scholar
  150. Shah P, Shah V (2007) Arginine supplementation for prevention of necrotising enterocolitis in preterm infants. Cochrane Database Syst Rev 3:CD004339Google Scholar
  151. Shamir R, Johnson WJ, Zolfaghari R, Lee HS, Fisher EA (1995) Role of bile salt-dependent cholesteryl ester hydrolase in the uptake of micellar cholesterol by intestinal cells. Biochemistry 34(19):6351–6358CrossRefPubMedGoogle Scholar
  152. Sharma R, Tepas JJ 3rd (2010) Microecology, intestinal epithelial barrier and necrotizing enterocolitis. Pediatr Surg Int 26(1):11–21CrossRefPubMedGoogle Scholar
  153. Sharma et al (2010) Microecology, intestinal epithelial barrier and necrotizing enterocolitis. Pediatr Surg Int 26:11–21. Scholar
  154. Sherman PM, Mitchell DJ, Cutz E (2004) Neonatal enteropathies: defining the causes of protracted diarrhea of infancy. J Pediatr Gastroenterol Nutr 38(1):16–26CrossRefPubMedGoogle Scholar
  155. Shulman RJ, Wong WW, Smith EO (2005) Influence of changes in lactase activity and small-intestinal mucosal growth on lactose digestion and absorption in preterm infants. Am J Clin Nutr 81(2):472–479CrossRefPubMedGoogle Scholar
  156. Siahanidou T, Mandyla H, Papassotiriou I, Anagnostakis D (2004) Serum lipids in preterm infants fed a formula supplemented with nucleotides. J Pediatr Gastroenterol Nutr 38(1):56–60CrossRefPubMedGoogle Scholar
  157. Siegle ML, Buhner S, Schemann M, Schmid HR, Ehrlein HJ (1990) Propagation velocities and frequencies of contractions along canine small intestine. Am J Physiol 258(5 Pt 1):G738–G744PubMedGoogle Scholar
  158. Simon-Assmann P, Turck N, Sidhoum-Jenny M, Gradwohl G, Kedinger M (2007) In vitro models of intestinal epithelial cell differentiation. Cell Biol Toxicol 23(4):241–256CrossRefPubMedGoogle Scholar
  159. Simpson C, Schanler RJ, Lau C (2002) Early introduction of oral feeding in preterm infants. Pediatrics 110(3):517–522CrossRefPubMedGoogle Scholar
  160. Sparks SE (2006) Inherited disorders of glycosylation. Mol Genet Metab 87(1):1–7CrossRefPubMedGoogle Scholar
  161. Srinivasjois R, Rao S, Patole S (2009) Prebiotic supplementation of formula in preterm neonates: a systematic review and meta-analysis of randomised controlled trials. Clin Nutr 28(3):237–242CrossRefPubMedGoogle Scholar
  162. Stahl A, Hirsch DJ, Gimeno RE, Punreddy S, Ge P, Watson N et al (1999) Identification of the major intestinal fatty acid transport protein. Mol Cell 4(3):299–308CrossRefPubMedGoogle Scholar
  163. Stark ME, Bauer AJ, Sarr MG, Szurszewski JH (1993) Nitric oxide mediates inhibitory nerve input in human and canine jejunum. Gastroenterology 104(2):398–409CrossRefPubMedGoogle Scholar
  164. Stevens BR, Preston RL (1998) Sodium-dependent amino acid transport is preserved in lyophilized reconstituted apical membranes from intestinal epithelium. Anal Biochem 265(1):117–122CrossRefPubMedGoogle Scholar
  165. Szajewska H, Skorka A, Ruszczynski M, Gieruszczak-Bialek D (2007) Meta-analysis: lactobacillus GG for treating acute diarrhoea in children. Aliment Pharmacol Ther 25(8):871–881CrossRefPubMedGoogle Scholar
  166. Tanaka M, Lee K, Martinez-Augustin O, He Y, Sanderson IR, Walker WA (1996) Exogenous nucleotides alter the proliferation, differentiation and apoptosis of human small intestinal epithelium. J Nutr 126(2):424–433CrossRefPubMedGoogle Scholar
  167. Thomson AB, Keelan M, Thiesen A, Clandinin MT, Ropeleski M, Wild GE (2001) Small bowel review: normal physiology part 1. Dig Dis Sci 46(12):2567–2587CrossRefPubMedGoogle Scholar
  168. Thureen P, Heird WC (2005) Protein and energy requirements of the preterm/low birthweight (LBW) infant. Pediatr Res 57(5 Pt 2):95R–98RCrossRefPubMedGoogle Scholar
  169. Underwood MA, Salzman NH, Bennett SH, Barman M, Mills D, Marcobal A et al (2009) A randomized placebo-controlled comparison of two prebiotic/probiotic combinations in preterm infants: Impact on weight gain, intestinal microbiota, and fecal short chain fatty acids. J Pediatr Gastroenterol Nutr 48(2):216–225PubMedCentralCrossRefPubMedGoogle Scholar
  170. Underwood MA, Kalanetra KM, Bokulich NA, Mirmiran M, Barile D, Tancredi DJ et al (2014) Prebiotic oligosaccharides in premature infants. J Pediatr Gastroenterol Nutr 58(3):352–360CrossRefPubMedGoogle Scholar
  171. VanderWall KJ, Bealer JF, Adzick NS, Harrison MR (1995) Cyclic GMP relaxes the internal anal sphincter in Hirschsprung’s disease. J Pediatr Surg 30(7):1013–1015CrossRefPubMedGoogle Scholar
  172. Vanderwinden JM, Liu H, De Laet MH, Vanderhaeghen JJ (1996a) Study of the interstitial cells of Cajal in infantile hypertrophic pyloric stenosis. Gastroenterology 111(2):279–288CrossRefPubMedGoogle Scholar
  173. Vanderwinden JM, Rumessen JJ, Liu H, Descamps D, De Laet MH, Vanderhaeghen JJ (1996b) Interstitial cells of Cajal in human colon and in Hirschsprung’s disease. Gastroenterology 111(4):901–910CrossRefPubMedGoogle Scholar
  174. Vanneste G, Van Nassauw NL, Kalfin R, Van Colen I, Elinck E, Van Crombruggen K et al (2008) Jejunal cholinergic, nitrergic, and soluble guanylate cyclase activity in postoperative ileus. Surgery 144(3):410–426CrossRefPubMedGoogle Scholar
  175. Villa M, Menard D, Semenza G, Mantei N (1992) The expression of lactase enzymatic activity and mRNA in human fetal jejunum. Effect of organ culture and of treatment with hydrocortisone. FEBS Lett 301(2):202–206CrossRefPubMedGoogle Scholar
  176. Vorbach C, Capecchi MR, Penninger JM (2006) Evolution of the mammary gland from the innate immune system? Bioessays 28(6):606–616CrossRefPubMedGoogle Scholar
  177. Walker WA (2002) Development of the intestinal mucosal barrier. J Pediatr Gastroenterol Nutr 34(Suppl 1):S33–S39CrossRefPubMedGoogle Scholar
  178. Wang PA, Huang FY (1994) Time of the first defaecation and urination in very low birth weight infants. Eur J Pediatr 153(4):279–283CrossRefPubMedGoogle Scholar
  179. Wenzl TG, Moroder C, Trachterna M, Thomson M, Silny J, Heimann G et al (2002) Esophageal pH monitoring and impedance measurement: a comparison of two diagnostic tests for gastroesophageal reflux. J Pediatr Gastroenterol Nutr 34(5):519–523CrossRefPubMedGoogle Scholar
  180. Wester T, O’Briain DS, Puri P (1999) Notable postnatal alterations in the myenteric plexus of normal human bowel. Gut 44(5):666–674PubMedCentralCrossRefPubMedGoogle Scholar
  181. Wiley JW, Lu YX, Owyang C (1991) Evidence for a glutamatergic neural pathway in the myenteric plexus. Am J Physiol 261(4 Pt 1):G693–G700PubMedGoogle Scholar
  182. Wong JM, de Souza R, Kendall CW, Emam A, Jenkins DJ (2006) Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol 40(3):235–243CrossRefPubMedGoogle Scholar
  183. Zangen S, Di Lorenzo C, Zangen T, Mertz H, Schwankovsky L, Hyman PE (2001) Rapid maturation of gastric relaxation in newborn infants. Pediatr Res 50(5):629–632CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeonatologyBnai Zion Medical Center, Rappaport Faculty of Medicine, Technion, Israel Institute of TechnologyHaifaIsrael
  2. 2.Pediatric Clinic, Department of Clinical Sciences and Community HealthUniversity of Milan Fondazione, IRCCS Ca Granda, Ospedale Maggiore PoliclinicoMilanoItaly
  3. 3.Institute of Gastroenterology Nutrition and Liver Diseases, Schneider Children’s Medical Center, Sackler Faculty of MedicineTel-Aviv UniversityPetach-TikvaIsrael

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