Advertisement

Impact of Microbes on the Intestinal Development of the Preterm Infant

  • Elizabeth Humphrey
  • Erika ClaudEmail author
Chapter
Part of the Physiology in Health and Disease book series (PIHD)

Abstract

The preterm intestine is not ready for life outside the womb because of its impaired digestive, absorptive, and motility capabilities. Intestinal barrier function is inadequate and enterocyte contributions to innate immunity are hyper-responsive, predisposing the infant to inflammatory disease and sepsis. Microbial colonization plays a significant role in normal postnatal development of the intestine. Microbial–host interactions can enhance motility, digestion, and absorption, in addition to strengthening barrier function and encouraging immune homeostasis. These benefits are not seen in preterm infants who experience delayed and altered microbial community colonization after birth, termed dysbiosis. In combination with the reduced gut functions in the preterm infant, dysbiosis can further damage existing gut functions and exacerbate the hyper-reactive inflammatory state, which increases the risk for inflammatory diseases such as necrotizing enterocolitis (NEC). This chapter details the role of the microbiome in intestinal maturation and outlines ways in which poor clinical outcomes in the preterm infant, such as NEC, could be circumvented through clinical interventions that optimize the microbiome community.

List of Abbreviations

BB

Brush border

BL

Basolateral

BM

Basement membrane

CI

Confidence interval

EEC

Enteroendocrine cell

EN

Enteric nutrition

ENS

Enteric nervous system

GALT

Gut-associated lymphoid tissue

GC

Goblet cell

GF

Germ-free

HMOs

Human milk oligosaccharides

IEC

Intestinal epithelial cell

LPS

Lipopolysaccharide

MAMPs

Microbial-associated molecular patterns

NEC

Necrotizing enterocolitis

NICU

Neonatal intensive care unit

NLR

NOD-like receptor

PC

Paneth cell

PN

Parenteral nutrition

RR

Relative risk

TJs

Tight junctions

TLR

Toll-like receptor

References

  1. Aceti A, Gori D, Barone G, Callegari ML, Di Mauro A, Fantini MP, Indrio F, Maggio L, Meneghin F, Morelli L, Zuccotti G, Corvaglia L (2015) Probiotics for prevention of necrotizing enterocolitis in preterm infants: systematic review and meta-analysis. Ital J Pediatr 41:89PubMedPubMedCentralCrossRefGoogle Scholar
  2. Adibi SA et al (1975) Evidence for two different modes of tripeptide disappearance in human intestine. Uptake by peptide carrier systems and hydrolysis by peptide hydrolases. J Clin Invest 56:1355–1363PubMedPubMedCentralCrossRefGoogle Scholar
  3. Agunod M, Yamaguchi N, Lopez R, Luhby AL, Glass GB (1969) Correlative study of hydrochloric acid, pepsin, and intrinsic factor secretion in newborns and infants. Am J Dig Dis 14:400–414PubMedCrossRefGoogle Scholar
  4. Ajslev TA, Andersen CS, Gamborg M, Sørensen TIA, Jess T (2011) Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics. Int J Obes (Lond) 35:522–529CrossRefGoogle Scholar
  5. Alemi B, Hamosh M, Scanlon JW, Salzman-Mann C, Hamosh P (1981) Fat digestion in very low-birth-weight infants: effect of addition of human milk to low-birth-weight formula. Pediatrics 68:484–489PubMedGoogle Scholar
  6. Alexander VN, Northrup V, Bizzarro MJ (2011) Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis. J Pediatr 159:392–397PubMedPubMedCentralCrossRefGoogle Scholar
  7. Anitha M, Vijay-Kumar M, Sitaraman SV, Gewirtz AT, Srinivasan S (2012) Gut microbial products regulate murine gastrointestinal motility via Toll-like receptor 4 signaling. Gastroenterology 143:1006–1016.e4PubMedPubMedCentralCrossRefGoogle Scholar
  8. Antonowicz I, Lebenthal E (1977) Developmental pattern of small intestinal enterokinase and disaccharidase activities in the human fetus. Gastroenterology 72:1299–1303PubMedGoogle Scholar
  9. Arboleya S, Binetti A, Salazar N, Fernández N, Solís G, Hernández-Barranco A, Margolles A, de los Reyes-Gavilán CG, Gueimonde M (2012) Establishment and development of intestinal microbiota in preterm neonates. FEMS Microbiol Ecol 79:763–772PubMedCrossRefGoogle Scholar
  10. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y et al (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331:337–341PubMedCrossRefGoogle Scholar
  11. Athalye-Jape G, Rao S, Patole S (2016) Lactobacillus reuteri DSM 17938 as a probiotic for preterm neonates: a strain-specific systematic review. J Parenter Enteral Nutr 40:783–794CrossRefGoogle Scholar
  12. Azad MB, Konya T, Maughan H, Guttman DS, Field CJ, Chari RS, Sears MR, Becker AB, Scott JA, Kozyrskyj AL (2013) Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ 185:385–394PubMedPubMedCentralCrossRefGoogle Scholar
  13. Barbara G, Stanghellini V, Brandi G, Cremon C, Di Nardo G, De Giorgio R, Corinaldesi R (2005) Interactions between commensal bacteria and gut sensorimotor function in health and disease. Am J Gastroenterol 100:2560–2568PubMedCrossRefGoogle Scholar
  14. Barrett M, Demehri FR, Teitelbaum DH (2015) Intestine, immunity and parenteral nutrition in an era of preferred enteral feeding. Curr Opin Clin Nutr Metab Care 18:496–500PubMedPubMedCentralCrossRefGoogle Scholar
  15. Bauer PV, Hamr SC, Duca FA (2015) Regulation of energy balance by a gut–brain axis and involvement of the gut microbiota. Cell Mol Life Sci 73:737–755PubMedCrossRefGoogle Scholar
  16. Beach RC, Menzies IS, Clayden GS, Scopes JW (1982) Gastrointestinal permeability changes in the preterm neonate. Arch Dis Child 57:141–145PubMedPubMedCentralCrossRefGoogle Scholar
  17. Beardmore HE, Rodgers BM, Outerbridge E (1978) Necrotizing enterocolitis (ischemic enteropathy) with the sequel of colonic atresia. Gastroenterology 74:914–917PubMedGoogle Scholar
  18. Berendsen PB, Blanchette-Mackie EJ (1979) Milk lipid absorption and chylomicron production in the suckling rat. Anat Rec 195:397–414PubMedCrossRefGoogle Scholar
  19. Berseth CL (1996) Gastrointestinal motility in the neonate. Clin Perinatol 23:179–190PubMedGoogle Scholar
  20. Berseth CL, Lichtenberger LM, Morriss FH (1983) Comparison of the gastrointestinal growth-promoting effects of rat colostrum and mature milk in newborn rats in vivo. Am J Clin Nutr 37:52–60PubMedCrossRefGoogle Scholar
  21. Berseth CL, Nordyke CK, Valdes MG, Furlow BL, Go VL (1992) Responses of gastrointestinal peptides and motor activity to milk and water feedings in preterm and term infants. Pediatr Res 31:587–590PubMedCrossRefGoogle Scholar
  22. Black DD, Rohwer-Nutter PL, Davidson NO (1990) Intestinal apolipoprotein A-IV gene expression in the piglet. J Lipid Res 31:497–505PubMedGoogle Scholar
  23. Brugman S, Perdijk O, van Neerven RJJ, Savelkoul HFJ (2015) Mucosal immune development in early life: setting the stage. Arch Immunol Ther Exp (Warsz) 63:251–268CrossRefGoogle Scholar
  24. Buddington RK, Malo C (1996) Intestinal brush-border membrane enzyme activities and transport functions during prenatal development of pigs. J Pediatr Gastroenterol Nutr 23:51–64PubMedCrossRefGoogle Scholar
  25. Buisine MP, Devisme L, Savidge TC, Gespach C, Gosselin B, Porchet N, Aubert JP (1998) Mucin gene expression in human embryonic and fetal intestine. Gut 43:519–524PubMedPubMedCentralCrossRefGoogle Scholar
  26. Burns AJ, Roberts RR, Bornstein JC, Young HM (2009) Development of the enteric nervous system and its role in intestinal motility during fetal and early postnatal stages. Semin Pediatr Surg 18:196–205PubMedCrossRefGoogle Scholar
  27. Butel M-J, Suau A, Campeotto F, Magne F, Aires J, Ferraris L, Kalach N, Leroux B, Dupont C (2007) Conditions of bifidobacterial colonization in preterm infants: a prospective analysis. J Pediatr Gastroenterol Nutr 44:577–582PubMedCrossRefGoogle Scholar
  28. Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts L, Naslain D, Neyrinck A, Lambert DM, Muccioli GG, Delzenne NM (2009) Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 58:1091–1103PubMedPubMedCentralCrossRefGoogle Scholar
  29. Chang J-C, Chen C-H, Fang L-J, Tsai C-R, Chang Y-C, Wang T-M (2013) Influence of prolonged storage process, pasteurization, and heat treatment on biologically-active human milk proteins. Pediatr Neonatol 54:360–366PubMedCrossRefGoogle Scholar
  30. Chu DM, Antony KM, Ma J, Prince AL, Showalter L, Moller M, Aagaard KM (2016) The early infant gut microbiome varies in association with a maternal high-fat diet. Genome Med 8:77PubMedPubMedCentralCrossRefGoogle Scholar
  31. Clark DA, Miller MJ (1990) Intraluminal pathogenesis of necrotizing enterocolitis. J Pediatr 117(1 Pt 2):S64–S67PubMedCrossRefGoogle Scholar
  32. Clark RH, Bloom BT, Spitzer AR, Gerstmann DR (2006) Reported medication use in the neonatal intensive care unit: data from a large national data set. Pediatrics 117:1979–1987PubMedCrossRefGoogle Scholar
  33. Claud EC, Walker WA (2001) Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis. FASEB J 15:1398–1403PubMedCrossRefGoogle Scholar
  34. Claud EC, Walker WA (2008) Bacterial colonization, probiotics, and necrotizing enterocolitis. J Clin Gastroenterol 42(Suppl 2):S46–S52PubMedCrossRefGoogle Scholar
  35. Claud EC, Lu L, Anton PM, Savidge T, Walker WA, Cherayil BJ (2004) Developmentally regulated IκB expression in intestinal epithelium and susceptibility to flagellin-induced inflammation. PNAS 101:7404–7408PubMedPubMedCentralCrossRefGoogle Scholar
  36. Claud EC, Keegan KP, Brulc JM, Lu L, Bartels D, Glass E, Chang EB, Meyer F, Antonopoulos DA (2013) Bacterial community structure and functional contributions to emergence of health or necrotizing enterocolitis in preterm infants. Microbiome 1:20PubMedPubMedCentralCrossRefGoogle Scholar
  37. Cleghorn G, Durie P, Benjamin L, Dati F (1988) The ontogeny of serum immunoreactive pancreatic lipase and cationic trypsinogen in the premature human infant. Biol Neonate 53:10–16PubMedCrossRefGoogle Scholar
  38. Collado MC, Isolauri E, Salminen S, Sanz Y (2009) The impact of probiotic on gut health. Curr Drug Metab 10:68–78PubMedCrossRefGoogle Scholar
  39. Collins J, Borojevic R, Verdu EF, Huizinga JD, Ratcliffe EM (2014) Intestinal microbiota influence the early postnatal development of the enteric nervous system. Neurogastroenterol Motil 26:98–107PubMedCrossRefGoogle Scholar
  40. Colony PC (1983) Successive phases of human fetal intestinal development. In: Kretchmer N, Miinkowski A (eds) Nutritional adaptation of the gastrointestinal tract of the newborn. Vevey/Raven, New York, pp 3–28Google Scholar
  41. Commare CE, Tappenden KA (2007) Development of the infant intestine: implications for nutrition support. Nutr Clin Pract 22:159–173PubMedCrossRefGoogle Scholar
  42. Cornick S, Tawiah A, Chadee K (2015) Roles and regulation of the mucus barrier in the gut. Tissue Barriers 3:e982426.  https://doi.org/10.4161/21688370.2014.982426 PubMedPubMedCentralCrossRefGoogle Scholar
  43. Costeloe K, Bowler U, Brocklehurst P, Hardy P, Heal P, Juszczak E et al (2016) A randomised controlled trial of the probiotic Bifidobacterium breve BBG-001 in preterm babies to prevent sepsis, necrotising enterocolitis and death: the Probiotics in Preterm Infants (PiPS) trial. Health Technol Assess 20:1–194PubMedPubMedCentralCrossRefGoogle Scholar
  44. Cotten CM, Taylor S, Stoll B, Goldberg RN, Hansen NI, Sanchez PJ, Ambalavanan N, Benjamin DK (2009) Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics 123:58–66PubMedPubMedCentralCrossRefGoogle Scholar
  45. Cristofalo EA, Schanler RJ, Blanco CL, Sullivan S, Trawoeger R, Kiechl-Kohlendorfer U, Dudell G, Rechtman DJ, Lee ML, Lucas A, Abrams S (2013) Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. J Pediatr 163:1592–1595PubMedCrossRefGoogle Scholar
  46. Davidson NO, Hausman AM, Ifkovits CA et al (1992) Human intestinal glucose transporter expression and localization of GLUT5. Am J Physiol 262:C795–C800PubMedCrossRefGoogle Scholar
  47. Demehri FR, Barrett M, Ralls MW, Miyasaka EA, Feng Y, Teitelbaum DH (2013) Intestinal epithelial cell apoptosis and loss of barrier function in the setting of altered microbiota with enteral nutrient deprivation. Front Cell Infect Microbiol 3:105PubMedPubMedCentralCrossRefGoogle Scholar
  48. Dewit O, Dibba B, Prentice A (1990) Breast-milk amylase activity in English and Gambian mothers: effects of prolonged lactation, maternal parity, and individual variations. Pediatr Res 28:502–506PubMedCrossRefGoogle Scholar
  49. Dilli D, Aydin B, Fettah ND, Özyazıcı E, Beken S, Zenciroğlu A, Okumuş N, Özyurt BM, İpek MŞ, Akdağ A, Turan Ö, Bozdağ Ş (2015) The propre-save study: effects of probiotics and prebiotics alone or combined on necrotizing enterocolitis in very low birth weight infants. J Pediatr 166:545–551.e1PubMedCrossRefGoogle Scholar
  50. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, Knight R (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. PNAS 107:11971–11975PubMedPubMedCentralCrossRefGoogle Scholar
  51. Dumont RC, Rudolph CD (1994) Development of gastrointestinal motility in the infant and chilD. Gastroenterol Clin North Am 23:655–671PubMedGoogle Scholar
  52. Egan CE, Sodhi CP, Good M, Lin J, Jia H, Yamaguchi Y et al (2016) Toll-like receptor 4–mediated lymphocyte influx induces neonatal necrotizing enterocolitis. J Clin Invest 126:495–508PubMedCrossRefGoogle Scholar
  53. Eggesbø M, Botten G, Stigum H, Nafstad P, Magnus P (2003) Is delivery by cesarean section a risk factor for food allergy? J Allergy Clin Immunol 112:420–426PubMedCrossRefGoogle Scholar
  54. Enss ML, Grosse-Siestrup H, Schmidt-Wittig U, Gärtner K (1992) Changes in colonic mucins of germfree rats in response to the introduction of a “normal” rat microbial flora. J Exp Anim Sci 35:110–119PubMedGoogle Scholar
  55. Fernandes J, Su W, Rahat-Rozenbloom S, Wolever TMS, Comelli EM (2014) Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans. Nutr Diab 4:e121.  https://doi.org/10.1038/nutD2014.23 CrossRefGoogle Scholar
  56. Furrie E, Macfarlane S, Kennedy A, Cummings JH, Walsh SV, O’Neil DA, Macfarlane GT (2005) Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut 54:242–249PubMedPubMedCentralCrossRefGoogle Scholar
  57. 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 49:589–593PubMedCrossRefGoogle Scholar
  58. Ganguli K, Meng D, Rautava S, Lu L, Walker WA, Nanthakumar N (2013) Probiotics prevent necrotizing enterocolitis by modulating enterocyte genes that regulate innate immune-mediated inflammation. Am J Physiol Gastrointest Liver Physiol 304:G132–G141PubMedCrossRefGoogle Scholar
  59. González-Ariki S, Husband AJ (2000) Ontogeny of IgA+ cells in lamina propria: effects of sympathectomy. Dev Comp Immunol 24:61–69PubMedCrossRefGoogle Scholar
  60. Greenwood C, Morrow AL, Lagomarcino AJ, Altaye M, Taft DH, Yu Z, Newburg DS, Ward DV, Schibler KR (2014) Early empiric antibiotic use in preterm infants is associated with lower bacterial diversity and higher relative abundance of Enterobacter. J Pediatr 165:23–29PubMedPubMedCentralCrossRefGoogle Scholar
  61. Gregory KE, Samuel BS, Houghteling P, Shan G, Ausubel FM, Sadreyev RI, Walker WA (2016) Influence of maternal breast milk ingestion on acquisition of the intestinal microbiome in preterm infants. Microbiome 4:68PubMedPubMedCentralCrossRefGoogle Scholar
  62. Gupta RW, Tran L, Norori J, Ferris MJ, Eren AM, Taylor CM, Dowd SE, Penn D (2013) Histamine-2 receptor blockers alter the fecal microbiota in premature infants. J Pediatr Gastroenterol Nutr 56:397–400PubMedCrossRefGoogle Scholar
  63. Hamosh M, Scanlon JW, Ganot D, Likel M, Scanlon KB, Hamosh P (1981) Fat digestion in the newborn. Characterization of lipase in gastric aspirates of premature and term infants. J Clin Invest 67:838–846PubMedPubMedCentralCrossRefGoogle Scholar
  64. Hapfelmeier S, Lawson MAE, Slack E, Kirundi JK, Stoel M et al (2010) Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science 328:1705–1709PubMedPubMedCentralCrossRefGoogle Scholar
  65. Harmsen HJ, Wildeboer-Veloo AC, Raangs GC et al (2000) Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. J Pediatr Gastroenterol Nutr 30:61–67PubMedCrossRefGoogle Scholar
  66. Hecht AL, Casterline BW, Earley ZM, Goo YA, Goodlett DR, Bubeck Wardenburg J (2016) Strain competition restricts colonization of an enteric pathogen and prevents colitis. EMBO Rep 17:1281–1291PubMedPubMedCentralCrossRefGoogle Scholar
  67. Hintz SR, Kendrick DE, Stoll BJ, Vohr BR, Fanaroff AA, Donovan EF, Poole WK, Blakely ML, Wright L, Higgins R (2005) Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics 115:696–703PubMedCrossRefGoogle Scholar
  68. Hooper LV, Littman DR, Macpherson AJ (2012) Interactions between the microbiota and the immune system. Science 336:1268–1273PubMedPubMedCentralCrossRefGoogle Scholar
  69. Hviid A, Svanström H, Frisch M (2011) Antibiotic use and inflammatory bowel diseases in childhood. Gut 60:49–54PubMedCrossRefGoogle Scholar
  70. Hyman PE, Clarke DD, Everett SL, Sonne B, Stewart D, Harada T, Walsh JH, Taylor IL (1985) Gastric acid secretory function in preterm infants. J Pediatr 106:467–471PubMedCrossRefGoogle Scholar
  71. Jakobsson HE, Abrahamsson TR, Jenmalm MC, Harris K, Quince C, Jernberg C, Björkstén B, Engstrand L, Andersson AF (2014) Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section. Gut 63:559–566PubMedCrossRefGoogle Scholar
  72. Johansson MEV, Ambort D, Pelaseyed T, Schütte A, Gustafsson JK, Ermund A et al (2011) Composition and functional role of the mucus layers in the intestine. Cell Mol Life Sci 68:3635–3641PubMedCrossRefGoogle Scholar
  73. Kandori H, Hirayama K, Takeda M, Doi K (1996) Histochemical, lectin-histochemical and morphometrical characteristics of intestinal goblet cells of germfree and conventional mice. Exp Anim 45:155–160PubMedCrossRefGoogle Scholar
  74. Kelly EJ, Newell SJ, Brownlee KG, Primrose JN, Dear PR (1993) Gastric acid secretion in preterm infants. Early Hum Dev 35:215–220PubMedCrossRefGoogle Scholar
  75. Kim YS, Ho SB (2010) Intestinal goblet cells and mucins in health and disease: recent insights and progress. Curr Gastroenterol Rep 12:319–330PubMedPubMedCentralCrossRefGoogle Scholar
  76. Koleva PT, Kim J-S, Scott JA, Kozyrskyj AL (2015) Microbial programming of health and disease starts during fetal life. Birth Defects Res C Embryo Today 105:265–277PubMedCrossRefGoogle Scholar
  77. La Rosa PS, Warner BB, Zhou Y, Weinstock GM, Sodergren E, Hall-Moore CM, Stevens HJ et al (2014) Patterned progression of bacterial populations in the premature infant gut. Proc Natl Acad Sci U S A 111:12522–12527PubMedPubMedCentralCrossRefGoogle Scholar
  78. Lacroix B et al (1984) Developmental pattern of brush border enzymes in the human fetal colon. Correlation with some morphogenetic events. Early Hum Dev 9:95–103PubMedCrossRefGoogle Scholar
  79. Leatham MP, Banerjee S, Autieri SM, Mercado-Lubo R, Conway T, Cohen PS (2009) Precolonized human commensal Escherichia coli strains serve as a barrier to E. coli O157:H7 growth in the streptomycin-treated mouse intestine. Infect Immun 77:2876–2886PubMedPubMedCentralCrossRefGoogle Scholar
  80. Lebenthal A, Lebenthal E (1999) The ontogeny of the small intestinal epithelium. J Parenter Enteral Nutr 23:S3–S6CrossRefGoogle Scholar
  81. Lebenthal E, Lee PC (1980) Development of functional responses in human exocrine pancreas. Pediatrics 66:556–560PubMedGoogle Scholar
  82. Lebenthal E, Rossi TM, Nord KS, Branski D (1981) Recurrent abdominal pain and lactose absorption in children. Pediatrics 67:828–832PubMedGoogle Scholar
  83. Lu L, Yu Y, Guo Y, Wang Y, Chang EB, Claud EC (2015) Transcriptional modulation of intestinal innate defense/inflammation genes by preterm infant microbiota in a humanized gnotobiotic mouse model. PLoS One 10:e0124504PubMedPubMedCentralCrossRefGoogle Scholar
  84. MacDonald TT, Spencer J (1994) Ontogeny of the gut-associated lymphoid system in man. Acta Paediatr Suppl 83:3–5PubMedCrossRefGoogle Scholar
  85. Madan JC, Farzan SF, Hibberd PL, Karagas MR (2012) Normal neonatal microbiome variation in relation to environmental factors, infection and allergy. Curr Opin Pediatr 24:753–759PubMedPubMedCentralCrossRefGoogle Scholar
  86. Mai V, Young CM, Ukhanova M, Wang X, Sun Y, Casella G, Theriaque D, Li N, Sharma R, Hudak M, Neu J (2011) Fecal microbiota in premature infants prior to necrotizing enterocolitis. PLoS One 6:e20647PubMedPubMedCentralCrossRefGoogle Scholar
  87. Malo C (1991) Multiple pathways for amino acid transport in brush border membrane vesicles isolated from the human fetal small intestine. Gastroenterology 100:1644–1652PubMedCrossRefGoogle Scholar
  88. Marcobal A, Sonnenburg JL (2012) Human milk oligosaccharide consumption by intestinal microbiota. Clin Microbiol Infect 18:12–15PubMedPubMedCentralCrossRefGoogle Scholar
  89. Maynard CL, Elson CO, Hatton RD, Weaver CT (2012) Reciprocal interactions of the intestinal microbiota and immune system. Nature 489:231–241PubMedPubMedCentralCrossRefGoogle Scholar
  90. Mazmanian SK, Round JL, Kasper DL (2008) A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453:620–625.  https://doi.org/10.1038/nature07008 PubMedCrossRefGoogle Scholar
  91. McVey Neufeld KA, Mao YK, Bienenstock J, Foster JA, Kunze WA (2013) The microbiome is essential for normal gut intrinsic primary afferent neuron excitability in the mouse. Neurogastroenterol Motil 25:183–e88PubMedCrossRefGoogle Scholar
  92. Meetze WH, Valentine C, McGuigan JE, Conlon M, Sacks N, Neu J (1992) Gastrointestinal priming prior to full enteral nutrition in very low birth weight infants. J Pediatr Gastroenterol Nutr 15:163–170PubMedCrossRefGoogle Scholar
  93. Meier P, Patel A, Esquerra-Zwiers A (2017) Donor human milk update: evidence, mechanisms, and priorities for research and practice. J Pediatr 180:15–21PubMedCrossRefGoogle Scholar
  94. Meinzen-Derr J, Poindexter B, Wrage L, Morrow AL, Stoll B, Donovan EF (2009) Role of human milk in extremely low birth weight infants’ risk of necrotizing enterocolitis or death. J Perinatol 29:57–62PubMedCrossRefGoogle Scholar
  95. Mellander L, Carlsson B, Jalil F, Söderström T, Hanson LA (1985) Secretory IgA antibody response against Escherichia coli antigens in infants in relation to exposure. J Pediatr 107:430–433PubMedCrossRefGoogle Scholar
  96. Montgomery RK et al (1999) Development of the human gastrointestinal tract: twenty years of progress. Gastroenterology 116:702–731PubMedCrossRefGoogle Scholar
  97. Moxey PC, Trier JS (1978) Specialized cell types in the human fetal small intestine. Anat Rec 191:269–285PubMedCrossRefGoogle Scholar
  98. Murk W, Risnes KR, Bracken MB (2011) Prenatal or early-life exposure to antibiotics and risk of childhood asthma: a systematic review. Pediatrics 127:1125–1138PubMedCrossRefGoogle Scholar
  99. Nahmias A, Stoll B, Hale E, Ibegbu C, Keyserling H, Innis-Whitehouse W, Holmes R, Spira T, Czerkinsky C, Lee F (1991) IgA-secreting cells in the blood of premature and term infants: normal development and effect of intrauterine infections. Adv Exp Med Biol 310:59–69PubMedCrossRefGoogle Scholar
  100. Nakamura N, Gaskins HR, Collier CT, Nava GM, Rai D, Petschow B et al (2009) Molecular ecological analysis of fecal bacterial populations from term infants fed formula supplemented with selected blends of prebiotics. Appl Environ Microbiol 75:1121–1128PubMedCrossRefGoogle Scholar
  101. Nanthakumar N, Meng D, Goldstein AM, Zhu W, Lu L, Uauy R, Llanos A, Claud EC, Walker WA (2011) The mechanism of excessive intestinal inflammation in necrotizing enterocolitis: an immature innate immune response. PLoS One 6:e17776PubMedPubMedCentralCrossRefGoogle Scholar
  102. Neish AS, Naumann M (2011) Microbial-induced immunomodulation by targeting the NF-κB system. Trends Microbiol 19:596–605PubMedCrossRefGoogle Scholar
  103. Neu J (2015) Developmental aspects of maternal-fetal, and infant gut microbiota and implications for long-term health. Matern Health Neonatol Perinatol 1:6PubMedPubMedCentralCrossRefGoogle Scholar
  104. Neu J, Walker WA (2011) Necrotizing enterocolitis. N Engl J Med 364:255–264PubMedPubMedCentralCrossRefGoogle Scholar
  105. Oeckinghaus A, Ghosh S (2009) The NF-κB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol 1:a000034PubMedPubMedCentralCrossRefGoogle Scholar
  106. Olsen R, Greisen G, Schrøder M, Brok J (2016) Prophylactic probiotics for preterm infants: a systematic review and meta-analysis of observational studies. Neonatology 109:105–112PubMedCrossRefGoogle Scholar
  107. Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO (2007) Development of the human infant intestinal microbiota. PLoS Biol 5:e177PubMedPubMedCentralCrossRefGoogle Scholar
  108. Park YK, Monaco MH, Donovan SM (1999) Enteral insulin-like growth factor-I augments intestinal disaccharidase activity in piglets receiving total parenteral nutrition. J Pediatr Gastroenterol Nutr 29:198–206PubMedCrossRefGoogle Scholar
  109. Patel RM, Myers LS, Kurundkar AR, Maheshwari A, Nusrat A, Lin PW (2012) Probiotic bacteria induce maturation of intestinal claudin 3 expression and barrier function. Am J Pathol 180:626–635PubMedPubMedCentralCrossRefGoogle Scholar
  110. Penn AH, Altshuler AE, Small JW, Taylor SF, Dobkins KR, Schmid-Schönbein GW (2012) Digested formula but not digested fresh human milk causes death of intestinal cells in vitro: implications for necrotizing enterocolitis. Pediatr Res 72:560–567PubMedPubMedCentralCrossRefGoogle Scholar
  111. Petersson J, Schreiber O, Hansson GC, Gendler SJ, Velcich A, Lundberg JO, Roos S, Holm L, Phillipson M (2011) Importance and regulation of the colonic mucus barrier in a mouse model of colitis. Am J Physiol Gastrointest Liver Physiol 300:G327–G333PubMedCrossRefGoogle Scholar
  112. Plaza-Zamora J, Sabater-Molina M, Rodríguez-Palmero M et al (2013) Polyamines in human breast milk for preterm and term infants. Br J Nutr 10:524–528CrossRefGoogle Scholar
  113. Poulsen SS, Kryger-Baggesen N, Nexø E (1996) Immunohistochemical localization of epidermal growth factor in the second-trimester human fetus. Histochem Cell Biol 105:111–117PubMedCrossRefGoogle Scholar
  114. Quigley M, McGuire W (2014) Formula versus donor breast milk for feeding preterm or low birth weight infants. Cochrane Database Syst Rev 22:CD002971Google Scholar
  115. Rakoff-Nahoum S, Hao L, Medzhitov R (2006) Role of toll-like receptors in spontaneous commensal-dependent colitis. Immunity 25:319–329PubMedCrossRefGoogle Scholar
  116. Raul F, Gosse F, Doffoel M, Darmenton P, Wessely JY (1988) Age related increase of brush border enzyme activities along the small intestine. Gut 29:1557–1563PubMedPubMedCentralCrossRefGoogle Scholar
  117. Reinhardt C, Reigstad CS, Bäckhed F (2009) Intestinal microbiota during infancy and its implications for obesity. J Pediatr Gastroenterol Nutr 48:249–256PubMedCrossRefGoogle Scholar
  118. Riezzo G, Indrio F, Raimondi F, Montagna O, Salvia G, Massimo B, Polimeno L, Cavallo L, Francavilla R (2009) Maturation of gastric electrical activity, gastric emptying and intestinal permeability in preterm newborns during the first month of life. Ital J Pediatr 35:6.  https://doi.org/10.1186/1824-7288-35-6 PubMedPubMedCentralCrossRefGoogle Scholar
  119. Rogier EW, Frantz AL, Bruno MEC, Wedlund L, Cohen DA, Stromberg AJ, Kaetzel CS (2014) Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression. Proc Natl Acad Sci U S A 111:3074–3079.  https://doi.org/10.1073/pnas.1315792111 PubMedPubMedCentralCrossRefGoogle Scholar
  120. Rondeau MP, Meltzer K, Michel KE, McManus CM, Washabau RJ (2003) Short chain fatty acids stimulate feline colonic smooth muscle contraction. J Feline Med Surg 5:167–173PubMedCrossRefGoogle Scholar
  121. Schanler RJ, Lau C, Hurst NM, Smith EO (2005) Randomized trial of donor human milk versus preterm formula as substitutes for mothers’ own milk in the feeding of extremely premature infants. Pediatrics 116:400–406PubMedCrossRefGoogle Scholar
  122. Sigge W, Wedel T, Kühnel W, Krammer HJ (1998) Morphologic alterations of the enteric nervous system and deficiency of non-adrenergic non-cholinergic inhibitory innervation in neonatal necrotizing enterocolitis. Eur J Pediatr Surg 8:87–94PubMedCrossRefGoogle Scholar
  123. Sisk PM, Lovelady CA, Dillard RG, Gruber KJ, O’Shea TM (2007) Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants. J Perinatol 27:428–433PubMedCrossRefGoogle Scholar
  124. Smith K, McCoy KD, Macpherson AJ (2007) Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin Immunol 19:59–69PubMedCrossRefGoogle Scholar
  125. Song SJ, Dominguez-Bello MG, Knight R (2013) How delivery mode and feeding can shape the bacterial community in the infant gut. Can Med Assoc J 185:373–374CrossRefGoogle Scholar
  126. Srinivasjois R, Rao S, Patole S (2013) Prebiotic supplementation in preterm neonates: updated systematic review and meta-analysis of randomised controlled trials. Clin Nutr 32:958–965PubMedCrossRefGoogle Scholar
  127. Taylor SN, Basile LA, Ebeling M, Wagner CL (2009) Intestinal permeability in preterm infants by feeding type: mother’s milk versus formula. Breastfeed Med 4:11–15PubMedPubMedCentralCrossRefGoogle Scholar
  128. Teitelbaum JE, Walker WA (2002) Nutritional impact of pre- and probiotics as protective gastrointestinal organisms. Annu Rev Nutr 22:107–138PubMedCrossRefGoogle Scholar
  129. Ter Beek WP, Muller ESM, van den Berg M, Meijer MJ, Biemond I, Lamers CB (2008) Motilin receptor expression in smooth muscle, myenteric plexus, and mucosa of human inflamed and noninflamed intestine. Inflamm Bowel Dis 14:612–619PubMedCrossRefGoogle Scholar
  130. Terrin G, Passariello A, Curtis MD, Manguso F, Salvia G, Lega L, Messina F, Paludetto R, Canani RB (2012) Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns. Pediatrics 129:e40–e45PubMedCrossRefGoogle Scholar
  131. Thibault L, Ménard D, Loirdighi N, Levy E (1992) Ontogeny of intestinal lipid and lipoprotein synthesis. Biol Neonate 62:100–107PubMedCrossRefGoogle Scholar
  132. Tormo-Badia N, Håkansson Å, Vasudevan K, Molin G, Ahrné S, Cilio CM (2014) Antibiotic treatment of pregnant non-obese diabetic mice leads to altered gut microbiota and intestinal immunological changes in the offspring. Scand J Immunol 80:250–260PubMedCrossRefGoogle Scholar
  133. Triadou N, Zweibaum A (1985) Maturation of sucrase-isomaltase complex in human fetal small and large intestine during gestation. Pediatr Res 19:136–138PubMedCrossRefGoogle Scholar
  134. Underwood MA, Kalanetra KM, Bokulich NA, Mirmiran M, Barile D, Tancredi DJ, German JB, Lebrilla CB, Mills DA (2014) Prebiotic oligosaccharides in premature infants. J Pediatr Gastroenterol Nutr 58:352–360PubMedCrossRefGoogle Scholar
  135. Underwood MA, German JB, Lebrilla CB, Mills DA (2015a) Bifidobacterium longum subspecies infantis: champion colonizer of the infant gut. Pediatr Res 77:229–235PubMedGoogle Scholar
  136. Underwood MA, Gaerlan S, De Leoz MLA, Dimapasoc L, Kalanetra KM, Lemay DG, German JB, Mills DA, Lebrilla CB (2015b) Human milk oligosaccharides in premature infants: absorption, excretion, and influence on the intestinal microbiota. Pediatr Res 78:670–677PubMedPubMedCentralCrossRefGoogle Scholar
  137. Van Itallie CM, Anderson JM (2014) Architecture of tight junctions and principles of molecular composition. Semin Cell Dev Biol 36:157–165PubMedCrossRefGoogle Scholar
  138. Vohr BR, Poindexter BB, Dusick AM, McKinley LT, Higgins RD, Langer JC, Poole WK, National Institute of Child Health and Human Development National Research Network (2007) Persistent beneficial effects of breast milk ingested in the neonatal intensive care unit on outcomes of extremely low birth weight infants at 30 months of age. Pediatrics 120:e953–e959PubMedCrossRefGoogle Scholar
  139. Vukavic T (1983) Intestinal absorption of IgA in the newborn. J Pediatr Gastroenterol Nutr 2:248–251PubMedCrossRefGoogle Scholar
  140. Wedel T, Krammer HJ, Kühnel W, Sigge W (1998) Alterations of the enteric nervous system in neonatal necrotizing enterocolitis revealed by whole-mount immunohistochemistry. Pediatr Pathol Lab Med 18:57–70PubMedCrossRefGoogle Scholar
  141. Xu RJ, Mellor DJ, Tungthanathanich P, Birtles MJ, Reynolds GW, Simpson HV (1992) Growth and morphological changes in the small and the large intestine in piglets during the first three days after birth. J Dev Physiol 18:161–172PubMedGoogle Scholar
  142. Yassour M, Vatanen T, Siljander H, Hämäläinen A-M, Härkönen T, Ryhänen SJ, Xavier RJ, DIABIMMUNE Study Group et al (2016) Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Sci Transl Med 8:343–381CrossRefGoogle Scholar
  143. Yu Z-T, Chen C, Kling DE, Liu B, McCoy JM, Merighi M, Heidtman M, Newburg DS (2013) The principal fucosylated oligosaccharides of human milk exhibit prebiotic properties on cultured infant microbiota. Glycobiology 23:169–177PubMedCrossRefGoogle Scholar
  144. Yu Y, Lu L, Sun J, Petrof EO, Claud EC (2016) Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model. Am J Physiol Gastrointest Liver Physiol 311:G521–G532PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© The American Physiological Society 2018

Authors and Affiliations

  1. 1.University of ChicagoChicagoUSA

Personalised recommendations