1932

Abstract

Pigs are increasingly important animals for modeling human pediatric nutrition and gastroenterology and complementing mechanistic studies in rodents. The comparative advantages in size and physiology of the neonatal pig have led to new translational and clinically relevant models of important diseases of the gastrointestinal tract and liver in premature infants. Studies in pigs have established the essential roles of prematurity, microbial colonization, and enteral nutrition in the pathogenesis of necrotizing enterocolitis. Studies in neonatal pigs have demonstrated the intestinal trophic effects of akey gut hormone, glucagon-like peptide 2 (GLP-2), and its role in the intestinal adaptation process and efficacy in the treatment of short bowel syndrome. Further, pigs have been instrumental in elucidating the physiology of parenteral nutrition–associated liver disease and the means by which phytosterols, fibroblast growth factor 19, and a new generation of lipid emulsions may modify disease. The premature pig will continue to be a valuable model in the development of optimal infant diets (donor human milk, colostrum), specific milk bioactives (arginine, growth factors), gut microbiota modifiers (pre-, pro-, and antibiotics), pharmaceutical drugs (GLP-2 analogs, FXR agonists), and novel diagnostic tools (near-infrared spectroscopy) to prevent and treat these pediatric diseases.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-animal-020518-115142
2020-02-15
2024-06-19
Loading full text...

Full text loading...

/deliver/fulltext/animal/8/1/annurev-animal-020518-115142.html?itemId=/content/journals/10.1146/annurev-animal-020518-115142&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Odle J, Lin X, Jacobi SK, Kim SW, Stahl CH 2014. The suckling piglet as an agrimedical model for the study of pediatric nutrition and metabolism. Annu. Rev. Anim. Biosci. 2:419–44
    [Google Scholar]
  2. 2. 
    Donovan SM, Odle J. 1994. Growth factors in milk as mediators of infant development. Annu. Rev. Nutr. 14:147–67
    [Google Scholar]
  3. 3. 
    Sangild PT, Ney DM, Sigalet DL, Vegge A, Burrin D 2014. Animal models of gastrointestinal and liver diseases. Animal models of infant short bowel syndrome: translational relevance and challenges. Am. J. Physiol. Gastrointest. Liver Physiol. 307:G1147–68
    [Google Scholar]
  4. 4. 
    Sangild PT, Thymann T, Schmidt M, Stoll B, Burrin DG, Buddington RK 2013. Invited review: the preterm pig as a model in pediatric gastroenterology. J. Anim. Sci. 91:4713–29
    [Google Scholar]
  5. 5. 
    Mudd AT, Dilger RN. 2017. Early-life nutrition and neurodevelopment: use of the piglet as a translational model. Adv. Nutr. 8:92–104
    [Google Scholar]
  6. 6. 
    Oosterloo BC, Premkumar M, Stoll B, Olutoye O, Thymann T et al. 2014. Dual purpose use of preterm pigs as a model of pediatric GI disease. Vet. Immunol. Immunopathol. 159:156–65
    [Google Scholar]
  7. 7. 
    Anderson JG, Baer RJ, Partridge JC, Kuppermann M, Franck LS et al. 2016. Survival and major morbidity of extremely preterm infants: a population-based study. Pediatrics 138:e20154434
    [Google Scholar]
  8. 8. 
    Kozuki N, Katz J, Christian P, Lee AC, Liu L et al. 2015. Comparison of US birth weight references and the International Fetal and Newborn Growth Consortium for the 21st century standard. JAMA Pediatr 169:e151438
    [Google Scholar]
  9. 9. 
    Glob. Burd. Dis. Pediatr. Collab Kyu HH, Pinho C, Wagner JA, Brown JC et al. 2016. Global and national burden of diseases and injuries among children and adolescents between 1990 and 2013: findings from the Global Burden of Disease 2013 study. JAMA Pediatr 170:267–87
    [Google Scholar]
  10. 10. 
    Kollmann TR, Kampmann B, Mazmanian SK, Marchant A, Levy O 2017. Protecting the newborn and young infant from infectious diseases: lessons from immune ontogeny. Immunity 46:350–63
    [Google Scholar]
  11. 11. 
    Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA et al. 2015. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993–2012. JAMA 314:1039–51
    [Google Scholar]
  12. 12. 
    Wales PW, Christison-Lagay ER. 2010. Short bowel syndrome: epidemiology and etiology. Semin. Pediatr. Surg. 19:3–9
    [Google Scholar]
  13. 13. 
    Hull MA, Fisher JG, Gutierrez IM, Jones BA, Kang KH et al. 2014. Mortality and management of surgical necrotizing enterocolitis in very low birth weight neonates: a prospective cohort study. J. Am. Coll. Surg. 218:1148–55
    [Google Scholar]
  14. 14. 
    Horbar JD, Ehrenkranz RA, Badger GJ, Edwards EM, Morrow KA et al. 2015. Weight growth velocity and postnatal growth failure in infants 501 to 1500 grams: 2000–2013. Pediatrics 136:e84–92
    [Google Scholar]
  15. 15. 
    Horbar JD, Carpenter JH, Badger GJ, Kenny MJ, Soll RF et al. 2012. Mortality and neonatal morbidity among infants 501 to 1500 grams from 2000 to 2009. Pediatrics 129:1019–26
    [Google Scholar]
  16. 16. 
    Horbar JD, Badger GJ, Carpenter JH, Fanaroff AA, Kilpatrick S et al. 2002. Trends in mortality and morbidity for very low birth weight infants, 1991–1999. Pediatrics 110:143–51
    [Google Scholar]
  17. 17. 
    Bjerre D, Mark T, Sorensen P, Proschowsky HF, Vernersen A et al. 2010. Investigation of candidate regions influencing litter size in Danish Landrace sows. J. Anim. Sci. 88:1603–9
    [Google Scholar]
  18. 18. 
    Che L, Thymann T, Bering SB, Le Huërou-Luron, D'Inca R et al. 2010. IUGR does not predispose to necrotizing enterocolitis or compromise postnatal intestinal adaptation in preterm pigs. Pediatr. Res. 67:54–59
    [Google Scholar]
  19. 19. 
    Ferenc K, Pietrzak P, Godlewski MM, Piwowarski J, Kilianczyk R et al. 2014. Intrauterine growth retarded piglet as a model for humans—studies on the perinatal development of the gut structure and function. Reprod. Biol. 14:51–60
    [Google Scholar]
  20. 20. 
    Caminita F, van der Merwe M, Hance B, Krishnan R, Miller S et al. 2015. A preterm pig model of lung immaturity and spontaneous infant respiratory distress syndrome. Am. J. Physiol. Lung Cell. Mol. Physiol. 308:L118–29
    [Google Scholar]
  21. 21. 
    Eiby YA, Wright LL, Kalanjati VP, Miller SM, Bjorkman ST et al. 2013. A pig model of the preterm neonate: anthropometric and physiological characteristics. PLOS ONE 8:e68763
    [Google Scholar]
  22. 22. 
    Christensen RD, Henry E, Wiedmeier SE, Burnett J, Lambert DK 2007. Identifying patients, on the first day of life, at high-risk of developing parenteral nutrition-associated liver disease. J. Perinatol. 27:284–90
    [Google Scholar]
  23. 23. 
    Wilmore DW, Dudrick SJ. 1968. Growth and development of an infant receiving all nutrients exclusively by vein. JAMA 203:860–64
    [Google Scholar]
  24. 24. 
    Embleton ND, Simmer K. 2014. Practice of parenteral nutrition in VLBW and ELBW infants. World Rev. Nutr. Diet. 110:177–89
    [Google Scholar]
  25. 25. 
    Buchman AL, Moukarzel AA, Bhuta S, Belle M, Ament ME et al. 1995. Parenteral nutrition is associated with intestinal morphologic and functional changes in humans. JPEN 19:453–60
    [Google Scholar]
  26. 26. 
    Rossi TM, Lee PC, Young C, Tjota A 1993. Small intestinal mucosa changes, including epithelial cell proliferative activity, of children receiving total parenteral nutrition (TPN). Dig. Dis. Sci. 38:1608–13
    [Google Scholar]
  27. 27. 
    Johnson LR, Copeland EM, Dudrick SJ, Lichtenberger LM, Castro GA 1975. Structural and hormonal alterations in the gastrointestinal tract of parenterally fed rats. Gastroenterology 68:1177–83
    [Google Scholar]
  28. 28. 
    Shulman RJ. 1988. Effect of different total parenteral nutrition fuel mixes on small intestinal growth and differentiation in the infant miniature pig. Gastroenterology 95:85–92
    [Google Scholar]
  29. 29. 
    Burrin DG, Stoll B, Jiang RH, Chang XY, Hartmann B et al. 2000. Minimal enteral nutrient requirements for intestinal growth in neonatal pigs: How much is enough?. Am. J. Clin. Nutr. 71:1603–10
    [Google Scholar]
  30. 30. 
    Burrin DG, Stoll B, Chang X, van Goudoever JB, Fujii H et al. 2003. Parenteral nutrition results in impaired lactose digestion and hexose absorption when enteral feeding is initiated in infant pigs. Am. J. Clin. Nutr. 78:461–70
    [Google Scholar]
  31. 31. 
    Kansagra K, Stoll B, Rognerud C, Niinikoski H, Ou CN et al. 2003. Total parenteral nutrition adversely affects gut barrier function in neonatal pigs. Am. J. Physiol. Gastrointest. Liver Physiol. 285:G1162–G70
    [Google Scholar]
  32. 32. 
    Niinikoski H, Stoll B, Guan X, Kansagra K, Lambert BD et al. 2004. Onset of small intestinal atrophy is associated with reduced intestinal blood flow in TPN-fed neonatal pigs. J. Nutr. 134:1467–74
    [Google Scholar]
  33. 33. 
    Ganessunker D, Gaskins HR, Zuckermann FA, Donovan SM 1999. Total parenteral nutrition alters molecular and cellular indices of intestinal inflammation in neonatal pigs. JPEN 23:337–44
    [Google Scholar]
  34. 34. 
    Conour JE, Ganessunker D, Tappenden KA, Donovan SM, Gaskins HR 2002. Acidomucin goblet cell expansion induced by parenteral nutrition in the small intestine of pigs. Am. J. Physiol. Gastrointest. Liver Physiol. 283:G1185–G96
    [Google Scholar]
  35. 35. 
    Deplancke B, Vidal O, Ganessunker D, Donovan SM, Mackie RI, Gaskins HR 2002. Selective growth of mucolytic bacteria including Clostridium perfringens in a neonatal piglet model of total parenteral nutrition. Am. J. Clin. Nutr. 76:1117–25
    [Google Scholar]
  36. 36. 
    Aynsley-Green A, Lucas A, Lawson GR, Bloom SR 1990. Gut hormones and regulatory peptides in relation to enteral feeding, gastroenteritis, and necrotizing enterocolitis in infancy. J. Pediatr. 117:S24–32
    [Google Scholar]
  37. 37. 
    Lucas A, Bloom SR, Aynsley-Green A 1986. Gut hormones and ‘minimal enteral feeding. Acta Paediatr. Scand. 75:719–23
    [Google Scholar]
  38. 38. 
    Berseth CL. 1995. Minimal enteral feedings. Clin. Perinatol. 22:195–205
    [Google Scholar]
  39. 39. 
    Shulman RJ, Schanler RJ, Lau C, Heitkemper M, Ou CN, Smith EO 1998. Early feeding, feeding tolerance, and lactase activity in preterm infants. J. Pediatr. 133:645–49
    [Google Scholar]
  40. 40. 
    Shulman RJ, Schanler RJ, Lau C, Heitkemper M, Ou CN, Smith EO 1998. Early feeding, antenatal glucocorticoids, and human milk decrease intestinal permeability in preterm infants. Pediatr. Res. 44:519–23
    [Google Scholar]
  41. 41. 
    Stoll B, Chang X, Fan MZ, Reeds PJ, Burrin DG 2000. Enteral nutrient intake level determines intestinal protein synthesis and accretion rates in neonatal pigs. Am. J. Physiol. Gastrointest. Liver Physiol. 279:G288–G94
    [Google Scholar]
  42. 42. 
    Ghoneim N, Bauchart-Thevret C, Oosterloo B, Stoll B, Kulkarni M et al. 2014. Delayed initiation but not gradual advancement of enteral formula feeding reduces the incidence of necrotizing enterocolitis (NEC) in preterm pigs. PLOS ONE 9:e106888
    [Google Scholar]
  43. 43. 
    Morgan J, Young L, McGuire W 2014. Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst. Rev. 8:CD001241
    [Google Scholar]
  44. 44. 
    Morgan J, Young L, McGuire W 2014. Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst. Rev. 12:CD001970
    [Google Scholar]
  45. 45. 
    Schanler RJ, Shulman RJ, Lau C 1999. Feeding strategies for premature infants: beneficial outcomes of feeding fortified human milk versus preterm formula. Pediatrics 103:1150–57
    [Google Scholar]
  46. 46. 
    Cristofalo EA, Schanler RJ, Blanco CL, Sullivan S, Trawoeger R et al. 2013. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. J. Pediatr. 163:1592–5.e1
    [Google Scholar]
  47. 47. 
    Gartner LM, Morton J, Lawrence RA, Naylor AJ, O'Hare D et al. 2005. Breastfeeding and the use of human milk. Pediatrics 115:496–506
    [Google Scholar]
  48. 48. 
    Moro GE, Arslanoglu S, Bertino E, Corvaglia L, Montirosso R et al. 2015. XII. Human milk in feeding premature infants: consensus statement. J. Pediatr. Gastroenterol. Nutr. 61:Suppl. 1S16–19
    [Google Scholar]
  49. 49. 
    Burrin DG, Shulman RJ, Reeds PJ, Davis TA, Gravitt KR 1992. Porcine colostrum and milk stimulate visceral organ and skeletal muscle protein synthesis in neonatal pigs. J. Nutr. 122:1205–13
    [Google Scholar]
  50. 50. 
    Burrin DG, Davis TA, Ebner S, Schoknecht PA, Fiorotto ML et al. 1995. Nutrient-independent and nutrient-dependent factors stimulate protein synthesis in colostrum-fed newborn pigs. Pediatr. Res. 37:593–99
    [Google Scholar]
  51. 51. 
    Burrin DG, Dudley MA, Reeds PJ, Shulman RJ, Perkinson S, Rosenberger J 1994. Feeding colostrum rapidly alters enzymatic activity and the relative isoform abundance of jejunal lactase in neonatal pigs. J. Nutr. 124:2350–57
    [Google Scholar]
  52. 52. 
    Thymann T, Burrin DG, Tappenden KA, Bjornvad CR, Jensen SK, Sangild PT 2006. Formula-feeding reduces lactose digestive capacity in neonatal pigs. Br. J. Nutr. 95:1075–81
    [Google Scholar]
  53. 53. 
    Sangild PT, Siggers RH, Schmidt M, Elnif J, Bjornvad CR et al. 2006. Diet- and colonization-dependent intestinal dysfunction predisposes to necrotizing enterocolitis in preterm pigs. Gastro-enterology 130:1776–92
    [Google Scholar]
  54. 54. 
    Bjornvad CR, Thymann T, Deutz NE, Burrin DG, Jensen SK et al. 2008. Enteral feeding induces diet-dependent mucosal dysfunction, bacterial proliferation, and necrotizing enterocolitis in preterm pigs on parenteral nutrition. Am. J. Physiol. Gastrointest. Liver Physiol. 295:G1092–G103
    [Google Scholar]
  55. 55. 
    Jensen ML, Sangild PT, Lykke M, Schmidt M, Boye M et al. 2013. Similar efficacy of human banked milk and bovine colostrum to decrease incidence of necrotizing enterocolitis in preterm pigs. Am. J. Physiol. Regul. Integr. Comp. Physiol. 305:R4–R12
    [Google Scholar]
  56. 56. 
    Shen RL, Thymann T, Ostergaard MV, Stoy AC, Krych L et al. 2015. Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs. Am. J. Physiol. Gastrointest. Liver Physiol. 309:G310–23
    [Google Scholar]
  57. 57. 
    Rasmussen SO, Martin L, Ostergaard MV, Rudloff S, Li Y et al. 2016. Bovine colostrum improves neonatal growth, digestive function, and gut immunity relative to donor human milk and infant formula in preterm pigs. Am. J. Physiol. Gastrointest. Liver Physiol. 311:G480–91
    [Google Scholar]
  58. 58. 
    Schanler RJ. 2007. Mother's own milk, donor human milk, and preterm formulas in the feeding of extremely premature infants. J. Pediatr. Gastroenterol. Nutr. 45:Suppl. 3S175–77
    [Google Scholar]
  59. 59. 
    Li Y, Nguyen DN, de Waard M, Christensen L, Zhou P et al. 2017. Pasteurization procedures for donor human milk affect body growth, intestinal structure, and resistance against bacterial infections in preterm pigs. J. Nutr. 147:1121–30
    [Google Scholar]
  60. 60. 
    O'Connor DL, Kiss A, Tomlinson C, Bando N, Bayliss A et al. 2018. Nutrient enrichment of human milk with human and bovine milk-based fortifiers for infants born weighing <1250 g: a randomized clinical trial. Am. J. Clin. Nutr. 108:108–16
    [Google Scholar]
  61. 61. 
    Sun J, Li Y, Nguyen DN, Mortensen MS, van den Akker CHP et al. 2018. Nutrient fortification of human donor milk affects intestinal function and protein metabolism in preterm pigs. J. Nutr. 148:336–47
    [Google Scholar]
  62. 62. 
    Li Y, Juhl SM, Ye X, Shen RL, Iyore EO et al. 2017. A stepwise, pilot study of bovine colostrum to supplement the first enteral feeding in preterm infants (Precolos): study protocol and initial results. Front. Pediatr. 5:42
    [Google Scholar]
  63. 63. 
    Nino DF, Sodhi CP, Hackam DJ 2016. Necrotizing enterocolitis: new insights into pathogenesis and mechanisms. Nat. Rev. Gastroenterol. Hepatol. 13:590–600
    [Google Scholar]
  64. 64. 
    Yee WH, Soraisham AS, Shah VS, Aziz K, Yoon W et al. 2012. Incidence and timing of presentation of necrotizing enterocolitis in preterm infants. Pediatrics 129:e298–304
    [Google Scholar]
  65. 65. 
    Caplan MS, Fanaroff A. 2017. Necrotizing: a historical perspective. Semin. Perinatol. 41:2–6
    [Google Scholar]
  66. 66. 
    Lu P, Sodhi CP, Jia H, Shaffiey S, Good M et al. 2014. Animal models of gastrointestinal and liver diseases. Animal models of necrotizing enterocolitis: pathophysiology, translational relevance, and challenges. Am. J. Physiol. Gastrointest. Liver Physiol. 306:G917–28
    [Google Scholar]
  67. 67. 
    Barlow B, Santulli TV, Heird WC, Pitt J, Blanc WA, Schullinger JN 1974. An experimental study of acute neonatal enterocolitis—the importance of breast milk. J. Pediatr. Surg. 9:587–95
    [Google Scholar]
  68. 68. 
    Premkumar MH, Sule G, Nagamani SC, Chakkalakal S, Nordin A et al. 2014. Argininosuccinate lyase in enterocytes protects from development of necrotizing enterocolitis. Am. J. Physiol. Gastrointest. Liver Physiol. 307:G347–54
    [Google Scholar]
  69. 69. 
    Touloukian RJ, Posch JN, Spencer R 1972. The pathogenesis of ischemic gastroenterocolitis of the neonate: selective gut mucosal ischemia in asphyxiated neonatal pigs. J. Pediatr. Surg. 7:194–205
    [Google Scholar]
  70. 70. 
    Di Lorenzo M, Bass J, Krantis A 1995. An intraluminal model of necrotizing enterocolitis in the developing neonatal piglet. J. Pediatr. Surg. 30:1138–42
    [Google Scholar]
  71. 71. 
    Nowicki PT. 2005. Ischemia and necrotizing enterocolitis: where, when, and how. Semin. Pediatr. Surg. 14:152–58
    [Google Scholar]
  72. 72. 
    Cohen IT, Nelson SD, Moxley RA, Hirsh MP, Counihan TC, Martin RF 1991. Necrotizing enterocolitis in a neonatal piglet model. J. Pediatr. Surg. 26:598–601
    [Google Scholar]
  73. 73. 
    Crissinger KD, Burney DL, Velasquez OR, Gonzalez E 1994. An animal model of necrotizing enterocolitis induced by infant formula and ischemia in developing pigs. Gastroenterology 106:1215–22
    [Google Scholar]
  74. 74. 
    Yu H, Hasan NM, In JG, Estes MK, Kovbasnjuk O et al. 2017. The contributions of human mini-intestines to the study of intestinal physiology and pathophysiology. Annu. Rev. Physiol. 79:291–312
    [Google Scholar]
  75. 75. 
    Senger S, Ingano L, Freire R, Anselmo A, Zhu W et al. 2018. Human fetal-derived enterospheres provide insights on intestinal development and a novel model to study necrotizing enterocolitis (NEC). Cell. Mol. Gastroenterol. Hepatol. 5:549–68
    [Google Scholar]
  76. 76. 
    Gonzalez LM, Moeser AJ, Blikslager AT 2015. Animal models of ischemia-reperfusion-induced intestinal injury: progress and promise for translational research. Am. J. Physiol. Gastrointest. Liver Physiol. 308:G63–G75
    [Google Scholar]
  77. 77. 
    Gonzalez LM, Williamson I, Piedrahita JA, Blikslager AT, Magness ST 2013. Cell lineage identification and stem cell culture in a porcine model for the study of intestinal epithelial regeneration. PLOS ONE 8:e66465
    [Google Scholar]
  78. 78. 
    Stieler Stewart A, Freund JM, Blikslager AT, Gonzalez LM 2018. Intestinal stem cell isolation and culture in a porcine model of segmental small intestinal ischemia. J. Vis. Exp. 135:e57647
    [Google Scholar]
  79. 79. 
    Robinson JL, Smith VA, Stoll B, Agarwal U, Premkumar MH et al. 2018. Prematurity reduces citrulline-arginine-nitric oxide production and precedes the onset of necrotizing enterocolitis in pigs. Am. J. Physiol. Gastrointest. Liver Physiol. 315:G638–G49
    [Google Scholar]
  80. 80. 
    Morgan J, Young L, McGuire W 2015. Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst. Rev. 8:CD001241
    [Google Scholar]
  81. 81. 
    Lucas A, Cole TJ. 1990. Breast milk and neonatal necrotising enterocolitis. Lancet 336:1519–23
    [Google Scholar]
  82. 82. 
    Li Y, Jensen ML, Chatterton DE, Jensen BB, Thymann T et al. 2013. Raw bovine milk improves gut responses to feeding relative to infant formula in preterm pigs. Am. J. Physiol. Gastrointest. Liver Physiol. 306:G81–90
    [Google Scholar]
  83. 83. 
    Donovan SM. 2016. The role of lactoferrin in gastrointestinal and immune development and function: a preclinical perspective. J. Pediatr. 173:Suppl.S16–28
    [Google Scholar]
  84. 84. 
    Burrin DG, Davis TA, Fiorotto ML, Reeds PJ 1997. Role of milk-borne versus endogenous insulin-like growth factor I in neonatal growth. J. Anim. Sci. 75:2739–43
    [Google Scholar]
  85. 85. 
    Pammi M, Suresh G. 2017. Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants. Cochrane Database Syst. Rev. 6:CD007137
    [Google Scholar]
  86. 86. 
    Shamir R, Kolacek S, Koletzko S, Tavori I, Bader D et al. 2009. Oral insulin supplementation in paediatric short bowel disease: a pilot observational study. J. Pediatr. Gastroenterol. Nutr. 49:108–11
    [Google Scholar]
  87. 87. 
    Shulman RJ. 2002. Effect of enteral administration of insulin on intestinal development and feeding tolerance in preterm infants: a pilot study. Arch. Dis. Child Fetal. Neonatal. Ed. 86:F131–33
    [Google Scholar]
  88. 88. 
    Burrin DG, Wester TJ, Davis TA, Amick S, Heath JP 1996. Orally administered IGF-I increases intestinal mucosal growth in formula-fed neonatal pigs. Am. J. Physiol. 270:R1085–91
    [Google Scholar]
  89. 89. 
    Park YK, Monaco MH, Donovan SM 1999. Enteral insulin-like growth factor-I augments intestinal disaccharidase activity in pigs receiving total parenteral nutrition. J. Pediatr. Gastroenterol. Nutr. 29:198–206
    [Google Scholar]
  90. 90. 
    Shulman RJ. 1990. Oral insulin increases small intestinal mass and disaccharidase activity in the newborn miniature pig. Pediatr. Res. 28:171–75
    [Google Scholar]
  91. 91. 
    Nguyen DN, Li Y, Sangild PT, Bering SB, Chatterton DE 2014. Effects of bovine lactoferrin on the immature porcine intestine. Br. J. Nutr. 111:321–31
    [Google Scholar]
  92. 92. 
    Reznikov EA, Comstock SS, Yi C, Contractor N, Donovan SM 2014. Dietary bovine lactoferrin increases intestinal cell proliferation in neonatal pigs. J. Nutr. 144:1401–8
    [Google Scholar]
  93. 93. 
    Burrin DG, Stoll B, Fan MZ, Dudley MA, Donovan SM, Reeds PJ 2001. Oral IGF-I alters the posttranslational processing but not the activity of lactase-phlorizin hydrolase in formula-fed neonatal pigs. J. Nutr. 131:2235–41
    [Google Scholar]
  94. 94. 
    Kien CL. 1996. Digestion, absorption, and fermentation of carbohydrates in the newborn. Clin. Perinatol. 23:211–28
    [Google Scholar]
  95. 95. 
    Shulman RJ. 1999. In vivo measurements of glucose absorption in preterm infants. Biol. Neonate 76:10–18
    [Google Scholar]
  96. 96. 
    Shulman RJ, Feste A, Ou C 1995. Absorption of lactose, glucose polymers, or combination in premature infants. J. Pediatr. 127:626–31
    [Google Scholar]
  97. 97. 
    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. 81:472–79
    [Google Scholar]
  98. 98. 
    Buddington RK, Sangild PT, Hance B, Huang EY, Black DD 2012. Prenatal gastrointestinal development in the pig and responses after preterm birth. J. Anim. Sci. 90:Suppl. 4290–98
    [Google Scholar]
  99. 99. 
    Griffin MP, Hansen JW. 1999. Can the elimination of lactose from formula improve feeding tolerance in premature infants?. J. Pediatr. 135:587–92
    [Google Scholar]
  100. 100. 
    Shulman RJ, Ou CN, Smith EO 2011. Evaluation of potential factors predicting attainment of full gavage feedings in preterm infants. Neonatology 99:38–44
    [Google Scholar]
  101. 101. 
    Kien CL. 1990. Colonic fermentation of carbohydrate in the premature infant: possible relevance to necrotizing enterocolitis. J. Pediatr. 117:S52–S58
    [Google Scholar]
  102. 102. 
    Montgomery RK, Mulberg AE, Grand RJ 1999. Development of the human gastrointestinal tract: twenty years of progress. Gastroenterology 116:702–31
    [Google Scholar]
  103. 103. 
    Thymann T, Moller HK, Stoll B, Stoy AC, Buddington RK et al. 2009. Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs. Am. J. Physiol. Gastrointest. Liver Physiol. 297:G1115–G25
    [Google Scholar]
  104. 104. 
    Buddington RK, Bering SB, Thymann T, Sangild PT 2008. Aldohexose malabsorption in preterm pigs is directly related to the severity of necrotizing enterocolitis. Pediatr. Res. 63:382–87
    [Google Scholar]
  105. 105. 
    Buddington RK, Davis SL, Buddington KK 2018. The risk of necrotizing enterocolitis differs among preterm pigs fed formulas with either lactose or maltodextrin. J. Pediatr. Gastroenterol. Nutr. 66:e61–e66
    [Google Scholar]
  106. 106. 
    Call L, Stoll B, Oosterloo B, Ajami N, Sheikh F et al. 2018. Metabolomic signatures distinguish the impact of formula carbohydrates on disease outcome in a preterm piglet model of NEC. Microbiome 6:111
    [Google Scholar]
  107. 107. 
    Nickerson KP, Chanin R, McDonald C 2015. Deregulation of intestinal anti-microbial defense by the dietary additive, maltodextrin. Gut Microbes 6:78–83
    [Google Scholar]
  108. 108. 
    Nickerson KP, Homer CR, Kessler SP, Dixon LJ, Kabi A et al. 2014. The dietary polysaccharide maltodextrin promotes Salmonella survival and mucosal colonization in mice. PLOS ONE 9:e101789
    [Google Scholar]
  109. 109. 
    Laudisi F, Di Fusco D, Dinallo V, Stolfi C, Di Grazia A et al. 2019. The food additive maltodextrin promotes endoplasmic reticulum stress-driven mucus depletion and exacerbates intestinal inflammation. Cell. Mol. Gastroenterol. Hepatol. 7:457–73
    [Google Scholar]
  110. 110. 
    Dasgupta S, Jain SK. 2017. Protective effects of amniotic fluid in the setting of necrotizing enterocolitis. Pediatr. Res. 82:584–95
    [Google Scholar]
  111. 111. 
    Good M, Siggers RH, Sodhi CP, Afrazi A, Alkhudari F et al. 2012. Amniotic fluid inhibits Toll-like receptor 4 signaling in the fetal and neonatal intestinal epithelium. PNAS 109:11330–35
    [Google Scholar]
  112. 112. 
    Zani A, Cananzi M, Fascetti-Leon F, Lauriti G, Smith VV et al. 2014. Preventing necrotising enterocolitis with amniotic fluid stem cells. Gut 63:218–19
    [Google Scholar]
  113. 113. 
    Siggers J, Ostergaard MV, Siggers RH, Skovgaard K, Molbak L et al. 2013. Postnatal amniotic fluid intake reduces gut inflammatory responses and necrotizing enterocolitis in preterm neonates. Am. J. Physiol. Gastrointest. Liver Physiol. 304:G864–75
    [Google Scholar]
  114. 114. 
    Ostergaard MV, Shen RL, Stoy AC, Skovgaard K, Krych L et al. 2016. Provision of amniotic fluid during parenteral nutrition increases weight gain with limited effects on gut structure, function, immunity, and microbiology in newborn preterm pigs. J. Parenter. Enter. Nutr. 40:552–66
    [Google Scholar]
  115. 115. 
    Charbonneau MR, Blanton LV, DiGiulio DB, Relman DA, Lebrilla CB et al. 2016. A microbial perspective of human developmental biology. Nature 535:48–55
    [Google Scholar]
  116. 116. 
    Pammi M, Cope J, Tarr PI, Warner BB, Morrow AL et al. 2017. Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis. Microbiome 5:31
    [Google Scholar]
  117. 117. 
    Nguyen DN, Fuglsang E, Jiang P, Birck MM, Pan X et al. 2016. Oral antibiotics increase blood neutrophil maturation and reduce bacteremia and necrotizing enterocolitis in the immediate postnatal period of preterm pigs. Innate Immun 22:51–62
    [Google Scholar]
  118. 118. 
    Birck MM, Nguyen DN, Cilieborg MS, Kamal SS, Nielsen DS et al. 2016. Enteral but not parenteral antibiotics enhance gut function and prevent necrotizing enterocolitis in formula-fed newborn preterm pigs. Am. J. Physiol. Gastrointest. Liver Physiol. 310:G323–33
    [Google Scholar]
  119. 119. 
    Cotten CM, Taylor S, Stoll B, Goldberg RN, Hansen NI et al. 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 123:58–66
    [Google Scholar]
  120. 120. 
    Greenberg RG, Chowdhury D, Hansen NI, Smith PB, Stoll BJ et al. 2019. Prolonged duration of early antibiotic therapy in extremely premature infants. Pediatr. Res. 85:994–1000
    [Google Scholar]
  121. 121. 
    Donovan SM, Comstock SS. 2016. Human milk oligosaccharides influence neonatal mucosal and systemic immunity. Ann. Nutr. Metab. 69:Suppl. 242–51
    [Google Scholar]
  122. 122. 
    Smilowitz JT, Lebrilla CB, Mills DA, German JB, Freeman SL 2014. Breast milk oligosaccharides: structure-function relationships in the neonate. Annu. Rev. Nutr. 34:143–69
    [Google Scholar]
  123. 123. 
    Pacheco AR, Barile D, Underwood MA, Mills DA 2015. The impact of the milk glycobiome on the neonate gut microbiota. Annu. Rev. Anim. Biosci. 3:419–45
    [Google Scholar]
  124. 124. 
    Bode L, Jantscher-Krenn E. 2012. Structure-function relationships of human milk oligosaccharides. Adv. Nutr. 3:383S–91S
    [Google Scholar]
  125. 125. 
    Davis EC, Wang M, Donovan SM 2017. The role of early life nutrition in the establishment of gastrointestinal microbial composition and function. Gut Microbes 8:143–71
    [Google Scholar]
  126. 126. 
    Rasmussen SO, Martin L, Ostergaard MV, Rudloff S, Roggenbuck M et al. 2017. Human milk oligosaccharide effects on intestinal function and inflammation after preterm birth in pigs. J. Nutr. Biochem. 40:141–54
    [Google Scholar]
  127. 127. 
    Cilieborg MS, Sangild PT, Jensen ML, Ostergaard MV, Christensen L et al. 2017. α1,2-Fucosyllactose does not improve intestinal function or prevent Escherichia coli F18 diarrhea in newborn pigs. J. Pediatr. Gastroenterol. Nutr. 64:310–18
    [Google Scholar]
  128. 128. 
    Cilieborg MS, Bering SB, Ostergaard MV, Jensen ML, Krych L et al. 2016. Minimal short-term effect of dietary 2′-fucosyllactose on bacterial colonisation, intestinal function and necrotising enterocolitis in preterm pigs. Br. J. Nutr. 116:834–41
    [Google Scholar]
  129. 129. 
    Tao N, Ochonicky KL, German JB, Donovan SM, Lebrilla CB 2010. Structural determination and daily variations of porcine milk oligosaccharides. J. Agric. Food Chem. 58:4653–59
    [Google Scholar]
  130. 130. 
    Comstock SS, Wang M, Hester SN, Li M, Donovan SM 2014. Select human milk oligosaccharides directly modulate peripheral blood mononuclear cells isolated from 10-d-old pigs. Br. J. Nutr. 111:819–28
    [Google Scholar]
  131. 131. 
    Li M, Monaco MH, Wang M, Comstock SS, Kuhlenschmidt TB et al. 2014. Human milk oligosaccharides shorten rotavirus-induced diarrhea and modulate piglet mucosal immunity and colonic microbiota. ISME J 8:1609–20
    [Google Scholar]
  132. 132. 
    Comstock SS, Li M, Wang M, Monaco MH, Kuhlenschmidt TB et al. 2017. Dietary human milk oligosaccharides but not prebiotic oligosaccharides increase circulating natural killer cell and mesenteric lymph node memory T cell populations in noninfected and rotavirus-infected neonatal pigs. J. Nutr. 147:1041–47
    [Google Scholar]
  133. 133. 
    Herfel TM, Jacobi SK, Lin X, Fellner V, Walker DC et al. 2011. Polydextrose enrichment of infant formula demonstrates prebiotic characteristics by altering intestinal microbiota, organic acid concentrations, and cytokine expression in suckling pigs. J. Nutr. 141:2139–45
    [Google Scholar]
  134. 134. 
    Underwood MA. 2019. Probiotics and the prevention of necrotizing enterocolitis. J. Pediatr. Surg. 54:405–12
    [Google Scholar]
  135. 135. 
    Chi C, Buys N, Li C, Sun J, Yin C 2018. Effects of prebiotics on sepsis, necrotizing enterocolitis, mortality, feeding intolerance, time to full enteral feeding, length of hospital stay, and stool frequency in preterm infants: a meta-analysis. Eur. J. Clin. Nutr. 73:657–70
    [Google Scholar]
  136. 136. 
    Siggers RH, Siggers J, Boye M, Thymann T, Molbak L et al. 2008. Early administration of probiotics alters bacterial colonization and limits diet-induced gut dysfunction and severity of necrotizing enterocolitis in preterm pigs. J. Nutr. 138:1437–44
    [Google Scholar]
  137. 137. 
    Good M, Sodhi CP, Ozolek JA, Buck RH, Goehring KC et al. 2014. Lactobacillus rhamnosus HN001 decreases the severity of necrotizing enterocolitis in neonatal mice and preterm pigs: evidence in mice for a role of TLR9. Am. J. Physiol. Gastrointest. Liver Physiol. 306:G1021–32
    [Google Scholar]
  138. 138. 
    Obelitz-Ryom K, Rendboe AK, Nguyen DN, Rudloff S, Brandt AB et al. 2018. Bovine milk oligosaccharides with sialyllactose for preterm pigs. Nutrients 10:1489
    [Google Scholar]
  139. 139. 
    Vaughn BP, Rank KM, Khoruts A 2019. Fecal microbiota transplantation: current status in treatment of GI and liver disease. Clin. Gastroenterol. Hepatol. 17:353–61
    [Google Scholar]
  140. 140. 
    Nicholson MR, Mitchell PD, Alexander E, Ballal S, Bartlett M et al. 2019. Efficacy of fecal microbiota transplantation for Clostridium difficile infection in children. Clin. Gastroenterol. Hepatol In press
    [Google Scholar]
  141. 141. 
    Brunse A, Martin L, Rasmussen TS, Christensen L, Skovsted Cilieborg M et al. 2019. Effect of fecal microbiota transplantation route of administration on gut colonization and host response in preterm pigs. ISME J 13:720–33
    [Google Scholar]
  142. 142. 
    Prado C, Michels M, Ávila P, Burger H, Milioli MVM, Dal-Pizzol F 2019. The protective effects of fecal microbiota transplantation in an experimental model of necrotizing enterocolitis. J. Pediatr. Surg. 54:1578–83
    [Google Scholar]
  143. 143. 
    Li X, Li X, Shang Q, Gao Z, Hao F et al. 2017. Fecal microbiota transplantation (FMT) could reverse the severity of experimental necrotizing enterocolitis (NEC) via oxidative stress modulation. Free Radic. Biol. Med. 108:32–43
    [Google Scholar]
  144. 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:G521–32
    [Google Scholar]
  145. 145. 
    Claud EC, Walker WA. 2001. Hypothesis: Inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis. FASEB J 15:1398–403
    [Google Scholar]
  146. 146. 
    Nanthakumar NN, Fusunyan RD, Sanderson I, Walker WA 2000. Inflammation in the developing human intestine: a possible pathophysiologic contribution to necrotizing enterocolitis. PNAS 97:6043–48
    [Google Scholar]
  147. 147. 
    Lotz M, Gutle D, Walther S, Menard S, Bogdan C, Hornef MW 2006. Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells. J. Exp. Med. 203:973–84
    [Google Scholar]
  148. 148. 
    Kramer BW, Ikegami M, Moss TJ, Nitsos I, Newnham JP, Jobe AH 2005. Endotoxin-induced chorioamnionitis modulates innate immunity of monocytes in preterm sheep. Am. J. Respir. Crit. Care Med. 171:73–77
    [Google Scholar]
  149. 149. 
    Newnham JP, Moss TJ, Kramer BW, Nitsos I, Ikegami M, Jobe AH 2002. The fetal maturational and inflammatory responses to different routes of endotoxin infusion in sheep. Am. J. Obstet. Gynecol. 186:1062–68
    [Google Scholar]
  150. 150. 
    Abreu MT, Fukata M, Arditi M 2005. TLR signaling in the gut in health and disease. J. Immunol. 174:4453–60
    [Google Scholar]
  151. 151. 
    Sun J, Fegan PE, Desai AS, Madara JL, Hobert ME 2007. Flagellin-induced tolerance of the Toll-like receptor 5 signaling pathway in polarized intestinal epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 292:G767–G78
    [Google Scholar]
  152. 152. 
    Reber KM, Nankervis CA, Nowicki PT 2002. Newborn intestinal circulation: physiology and pathophysiology. Clin. Perinatol. 29:23–39
    [Google Scholar]
  153. 153. 
    Watkins DJ, Besner GE. 2013. The role of the intestinal microcirculation in necrotizing enterocolitis. Semin. Pediatr. Surg. 22:83–87
    [Google Scholar]
  154. 154. 
    Shepherd AP. 1982. Local control of intestinal oxygenation and blood flow. Annu. Rev. Physiol. 44:13–27
    [Google Scholar]
  155. 155. 
    Zheng L, Kelly CJ, Colgan SP 2015. Physiologic hypoxia and oxygen homeostasis in the healthy intestine. A review in the theme: cellular responses to hypoxia. Am. J. Physiol. Cell Physiol. 309:C350–C60
    [Google Scholar]
  156. 156. 
    Alward CT, Hook JB, Helmrath TA, Mattson JC, Bailie MD 1978. Effects of asphyxia on cardiac output and organ blood flow in the newborn piglet. Pediatr. Res. 12:824–27
    [Google Scholar]
  157. 157. 
    Behrman RE, Stoll BJ, Kanto WP Jr, Glass RI, Nahmias AJ, Brann AW Jr 1980. Epidemiology of necrotizing enterocolitis: a case control study. J. Pediatr 96:447–51
    [Google Scholar]
  158. 158. 
    Seeman SM, Mehal JM, Haberling DL, Holman RC, Stoll BJ 2016. Infant and maternal risk factors related to necrotising enterocolitis-associated infant death in the United States. Acta Paediatr. Int. J. Paediatr. 105:e240–e46
    [Google Scholar]
  159. 159. 
    Berkhout DJC, Klaassen P, Niemarkt HJ, De Boode WP, Cossey V et al. 2018. Risk factors for necrotizing enterocolitis: a prospective multicenter case-control study. Neonatology 114:277–84
    [Google Scholar]
  160. 160. 
    Chen YM, Zhang JS, Duan XL 2003. Changes of microvascular architecture, ultrastructure and permeability or rat jejunal villi at different ages. World J. Gastroenterol. 9:795–99
    [Google Scholar]
  161. 161. 
    Gosche JR, Harris PD, Garrison RN 1993. Age-related differences in intestinal microvascular responses to low-flow states in adult and suckling rats. Am. J. Physiol. Gastrointest. Liver Physiol. 264:G447–G53
    [Google Scholar]
  162. 162. 
    Nankervis CA, Schauer GM, Miller CE 2000. Endothelin-mediated vasoconstriction in postischemic newborn intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 279:G683–G91
    [Google Scholar]
  163. 163. 
    Nowicki PT, Dunaway DJ, Nankervis CA, Giannnone PJ, Reber KM et al. 2005. Endothelin-1 in human intestine resected for necrotizing enterocolitis. J. Pediatr. 146:805–10
    [Google Scholar]
  164. 164. 
    Nowicki PT, Caniano DA, Hammond S, Giannone PJ, Besner GE et al. 2007. Endothelial nitric oxide synthase in human intestine resected for necrotizing enterocolitis. J. Pediatr. 150:40–45
    [Google Scholar]
  165. 165. 
    Shah PS, Shah VS, Kelly LE 2017. Arginine supplementation for prevention of necrotising enterocolitis in preterm infants. Cochrane Database Syst. Rev. 4:CD004339
    [Google Scholar]
  166. 166. 
    Marini JC, Agarwal U, Robinson JL, Yuan Y, Didelija IC et al. 2017. The intestinal-renal axis for arginine synthesis is present and functional in the neonatal pig. Am. J. Physiol. Endocrinol. Metab. 313:E233–E42
    [Google Scholar]
  167. 167. 
    Puiman PJ, Stoll B, van Goudoever JB, Burrin DG 2011. Enteral arginine does not increase superior mesenteric arterial blood flow but induces mucosal growth in neonatal pigs. J. Nutr. 141:63–70
    [Google Scholar]
  168. 168. 
    Colgan SP, Campbell EL, Kominsky DJ 2016. Hypoxia and mucosal inflammation. Annu. Rev. Pathol. Mech. Dis. 11:77–100
    [Google Scholar]
  169. 169. 
    Hansen CF, Thymann T, Andersen AD, Holst JJ, Hartmann B et al. 2016. Rapid gut growth but persistent delay in digestive function in the postnatal period of preterm pigs. Am. J. Physiol. Gastrointest. Liver Physiol. 310:G550–G60
    [Google Scholar]
  170. 170. 
    Bjornvad CR, Schmidt M, Petersen YM, Jensen SK, Offenberg H et al. 2005. Preterm birth makes the immature intestine sensitive to feeding-induced intestinal atrophy. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289:R1212–R22
    [Google Scholar]
  171. 171. 
    Gribar SC, Anand RJ, Sodhi CP, Hackam DJ 2008. The role of epithelial Toll-like receptor signaling in the pathogenesis of intestinal inflammation. J. Leukoc. Biol. 83:493–98
    [Google Scholar]
  172. 172. 
    Siggers J, Sangild PT, Jensen TK, Siggers RH, Skovgaard K et al. 2011. Transition from parenteral to enteral nutrition induces immediate diet-dependent gut histological and immunological responses in preterm neonates. Am. J. Physiol. Gastrointest. Liver Physiol. 301:G435–45
    [Google Scholar]
  173. 173. 
    Gribar SC, Sodhi CP, Richardson WM, Anand RJ, Gittes GK et al. 2009. Reciprocal expression and signaling of TLR4 and TLR9 in the pathogenesis and treatment of necrotizing enterocolitis. J. Immunol. 182:636–46
    [Google Scholar]
  174. 174. 
    Garvey AA, Dempsey EM. 2018. Applications of near infrared spectroscopy in the neonate. Curr. Opin. Pediatr. 30:209–15
    [Google Scholar]
  175. 175. 
    Wyatt JS, Delpy DT, Cope M, Wray S, Reynolds EOR 1986. Quantification of cerebral oxygenation and haemodynamics in sick newborn infants by near infrared spectrophotometry. Lancet 328:1063–66
    [Google Scholar]
  176. 176. 
    Martini S, Corvaglia L. 2018. Splanchnic NIRS monitoring in neonatal care: rationale, current applications and future perspectives. J. Perinatol. 38:431–43
    [Google Scholar]
  177. 177. 
    Zamora IJ, Stoll B, Ethun CG, Sheikh F, Yu L et al. 2015. Low abdominal NIRS values and elevated plasma intestinal fatty acid-binding protein in a premature piglet model of necrotizing enterocolitis. PLOS ONE 10:e0125437
    [Google Scholar]
  178. 178. 
    Chen MW, Reyes M, Kulikowicz E, Martin L, Hackam DJ et al. 2018. Abdominal near-infrared spectroscopy in a piglet model of gastrointestinal hypoxia produced by graded hypoxia or superior mesenteric artery ligation. Pediatr. Res. 83:1172–81
    [Google Scholar]
  179. 179. 
    Gay AN, Lazar DA, Stoll B, Naik-Mathuria B, Mushin OP et al. 2011. Near-infrared spectroscopy measurement of abdominal tissue oxygenation is a useful indicator of intestinal blood flow and necrotizing enterocolitis in premature pigs. J. Pediatr. Surg. 46:1034–40
    [Google Scholar]
  180. 180. 
    Patel AK, Lazar DA, Burrin DG, Smith EO, Magliaro TJ et al. 2014. Abdominal near-infrared spectroscopy measurements are lower in preterm infants at risk for necrotizing enterocolitis. Pediatr. Crit. Care Med. 15:735–41
    [Google Scholar]
  181. 181. 
    Squires RH, Duggan C, Teitelbaum DH, Wales PW, Balint J et al. 2012. Natural history of pediatric intestinal failure: initial report from the Pediatric Intestinal Failure Consortium. J. Pediatr. 161:723–28.e2
    [Google Scholar]
  182. 182. 
    Dowling RH. 2003. Glucagon-like peptide-2 and intestinal adaptation: an historical and clinical perspective. J. Nutr. 133:3703–7
    [Google Scholar]
  183. 183. 
    Weih S, Nickkholgh A, Kessler M, Frongia G, Hafezi M et al. 2013. Models of short bowel syndrome in pigs: a technical review. Eur. Surg. Res. 51:66–78
    [Google Scholar]
  184. 184. 
    Turner JM, Wales PW, Nation PN, Wizzard P, Pendlebury C et al. 2011. Novel neonatal piglet models of surgical short bowel syndrome with intestinal failure. J. Pediatr. Gastroenterol. Nutr. 52:9–16
    [Google Scholar]
  185. 185. 
    Bartholome AL, Albin DM, Baker DH, Holst JJ, Tappenden KA 2004. Supplementation of total parenteral nutrition with butyrate acutely increases structural aspects of intestinal adaptation after an 80% jejunoileal resection in neonatal pigs. J. Parenter. Enter. Nutr. 28:210–22; discussion 22–23
    [Google Scholar]
  186. 186. 
    Pereira-Fantini PM, Lapthorne S, Gahan CGM, Joyce SA, Charles J et al. 2017. Farnesoid X receptor agonist treatment alters bile acid metabolism but exacerbates liver damage in a piglet model of short-bowel syndrome. Cell. Mol. Gastroenterol. Hepatol. 4:65–74
    [Google Scholar]
  187. 187. 
    Pereira-Fantini PM, Lapthorne S, Joyce SA, Dellios NL, Wilson G et al. 2014. Altered FXR signalling is associated with bile acid dysmetabolism in short bowel syndrome-associated liver disease. J. Hepatol. 61:1115–25
    [Google Scholar]
  188. 188. 
    Lin S, Stoll B, Robinson J, Pastor JJ, Marini JC et al. 2019. Differential action of TGR5 agonists on GLP-2 secretion and promotion of intestinal adaptation in piglet short bowel model. Am. J. Physiol. Gastrointest. Liver Physiol. 316:G641–52
    [Google Scholar]
  189. 189. 
    Pereira-Fantini PM, Thomas SL, Wilson G, Taylor RG, Sourial M, Bines JE 2011. Short- and long-term effects of small bowel resection: a unique histological study in a piglet model of short bowel syndrome. Histochem. Cell Biol. 135:195–202
    [Google Scholar]
  190. 190. 
    Vegge A, Thymann T, Lund P, Stoll B, Bering SB et al. 2013. Glucagon-like peptide-2 induces rapid digestive adaptation following intestinal resection in preterm neonates. Am. J. Physiol. Gastrointest. Liver Physiol. 305:G277–85
    [Google Scholar]
  191. 191. 
    Naberhuis JK, Deutsch AS, Tappenden KA 2017. Teduglutide-stimulated intestinal adaptation is complemented and synergistically enhanced by partial enteral nutrition in a neonatal piglet model of short bowel syndrome. J. Parenter. Enter. Nutr. 41:853–65
    [Google Scholar]
  192. 192. 
    Hua Z, Turner JM, Sigalet DL, Wizzard PR, Nation PN et al. 2013. Role of glucagon-like peptide-2 deficiency in neonatal short-bowel syndrome using neonatal pigs. Pediatr. Res. 73:742–49
    [Google Scholar]
  193. 193. 
    Pereira-Fantini PM, Thomas SL, Taylor RG, Nagy E, Sourial M et al. 2008. Colostrum supplementation restores insulin-like growth factor -1 levels and alters muscle morphology following massive small bowel resection. J. Parenter. Enter. Nutr. 32:266–75
    [Google Scholar]
  194. 194. 
    Goulet O, Olieman J, Ksiazyk J, Spolidoro J, Tibboe D et al. 2013. Neonatal short bowel syndrome as a model of intestinal failure: physiological background for enteral feeding. Clin. Nutr. 32:162–71
    [Google Scholar]
  195. 195. 
    Aunsholt L, Jeppesen PB, Lund P, Sangild PT, Ifaoui IB et al. 2014. Bovine colostrum to children with short bowel syndrome: a randomized, double-blind, crossover pilot study. J. Parenter. Enter. Nutr. 38:99–106
    [Google Scholar]
  196. 196. 
    Aunsholt L, Qvist N, Sangild PT, Vegge A, Stoll B et al. 2017. Minimal enteral nutrition to improve adaptation after intestinal resection in pigs and infants. J. Parenter. Enter. Nutr. 42:446–54
    [Google Scholar]
  197. 197. 
    Jeppesen PB, Pertkiewicz M, Messing B, Iyer K, Seidner DL et al. 2012. Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology 143:1473–81.e3
    [Google Scholar]
  198. 198. 
    Carter BA, Cohran VC, Cole CR, Corkins MR, Dimmitt RA et al. 2017. Outcomes from a 12-week, open-label, multicenter clinical trial of teduglutide in pediatric short bowel syndrome. J. Pediatr. 181:102–11.e5
    [Google Scholar]
  199. 199. 
    Guan X, Karpen HE, Stephens J, Bukowski JT, Niu S et al. 2006. GLP-2 receptor localizes to enteric neurons and endocrine cells expressing vasoactive peptides and mediates increased blood flow. Gastroenterology 130:150–64
    [Google Scholar]
  200. 200. 
    Guan XF, Stoll B, Lu XF, Tappenden KA, Holst JJ et al. 2003. GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed pigs. Gastroenterology 125:136–47
    [Google Scholar]
  201. 201. 
    Stephens J, Stoll B, Cottrell J, Chang X, Helmrath M, Burrin DG 2006. Glucagon-like peptide-2 acutely increases proximal small intestinal blood flow in TPN-fed neonatal pigs. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290:R283–R89
    [Google Scholar]
  202. 202. 
    Burrin DG, Stoll B, Guan X, Cui L, Chang X, Hadsell D 2007. GLP-2 rapidly activates divergent intracellular signaling pathways involved in intestinal cell survival and proliferation in neonatal pigs. Am. J. Physiol. Endocrinol. Metab. 292:E281–E91
    [Google Scholar]
  203. 203. 
    Burrin DG, Stoll B, Guan X, Cui L, Chang X, Holst JJ 2005. Glucagon-like peptide 2 dose-dependently activates intestinal cell survival and proliferation in neonatal pigs. Endocrinology 146:22–32
    [Google Scholar]
  204. 204. 
    Burrin DG, Stoll B, Jiang R, Petersen Y, Elnif J et al. 2000. GLP-2 stimulates intestinal growth in premature TPN-fed pigs by suppressing proteolysis and apoptosis. Am. J. Physiol. Gastrointest. Liver Physiol. 279:G1249–G56
    [Google Scholar]
  205. 205. 
    Cottrell JJ, Stoll B, Buddington RK, Stephens JE, Cui L et al. 2006. Glucagon-like peptide-2 protects against TPN-induced intestinal hexose malabsorption in enterally refed pigs. Am. J. Physiol. Gastrointest. Liver Physiol. 290:G293–300
    [Google Scholar]
  206. 206. 
    Sigalet DL, de Heuvel E, Wallace L, Bulloch E, Turner J et al. 2014. Effects of chronic glucagon-like peptide-2 therapy during weaning in neonatal pigs. Regul. Pept. 188:70–80
    [Google Scholar]
  207. 207. 
    Amin H, Holst JJ, Hartmann B, Wallace L, Wright J, Sigalet DL 2008. Functional ontogeny of the proglucagon-derived peptide axis in the premature human neonate. Pediatrics 121:e180–86
    [Google Scholar]
  208. 208. 
    Barnes JL, Hartmann B, Holst JJ, Tappenden KA 2012. Intestinal adaptation is stimulated by partial enteral nutrition supplemented with the prebiotic short-chain fructooligosaccharide in a neonatal intestinal failure piglet model. J. Parenter. Enter. Nutr. 36:524–37
    [Google Scholar]
  209. 209. 
    Slim GM, Lansing M, Wizzard P, Nation PN, Wheeler SE et al. 2019. Novel long-acting GLP-2 analogue, FE 203799 (apraglutide), enhances adaptation and linear intestinal growth in a neonatal piglet model of short bowel syndrome with total resection of the ileum. J. Parenter. Enter. Nutr. 43:891–98
    [Google Scholar]
  210. 210. 
    Thymann T, Stoll B, Mecklenburg L, Burrin DG, Vegge A et al. 2014. Acute effects of the glucagon-like peptide 2 analogue, teduglutide, on intestinal adaptation in short bowel syndrome. J. Pediatr. Gastroenterol. Nutr. 58:694–702
    [Google Scholar]
  211. 211. 
    Suri M, Turner JM, Sigalet DL, Wizzard PR, Nation PN, et al. 2014. Exogenous glucagon-like peptide-2 improves outcomes of intestinal adaptation in a distal-intestinal resection neonatal piglet model of short bowel syndrome. Pediatr. Res. 76:370–77
    [Google Scholar]
  212. 212. 
    Lim DW, Diane A, Muto M, Vine DF, Nation PN et al. 2017. Differential effects on intestinal adaptation following exogenous glucagon-like peptide 2 therapy with and without enteral nutrition in neonatal short bowel syndrome [formula: see text]. J. Parenter. Enter. Nutr. 41:156–70
    [Google Scholar]
  213. 213. 
    Naimi RM, Hvistendahl M, Enevoldsen LH, Madsen JL, Fuglsang S et al. 2019. Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome: a randomised phase 2 trial. Lancet Gastroenterol. Hepatol. 4:354–63
    [Google Scholar]
  214. 214. 
    Rowland KJ, Trivedi S, Lee D, Wan K, Kulkarni RN et al. 2011. Loss of glucagon-like peptide-2-induced proliferation following intestinal epithelial insulin-like growth factor-1-receptor deletion. Gastroenterology 141:2166–75.e7
    [Google Scholar]
  215. 215. 
    Drucker DJ, Habener JF, Holst JJ 2017. Discovery, characterization, and clinical development of the glucagon-like peptides. J. Clin. Investig. 127:4217–27
    [Google Scholar]
  216. 216. 
    Lim DW, Levesque CL, Vine DF, Muto M, Koepke JR et al. 2017. Synergy of glucagon-like peptide-2 and epidermal growth factor coadministration on intestinal adaptation in neonatal pigs with short bowel syndrome. Am. J. Physiol. Gastrointest. Liver Physiol. 312:G390–G404
    [Google Scholar]
  217. 217. 
    Jain AK, Stoll B, Burrin DG, Holst JJ, Moore DD 2012. Enteral bile acid treatment improves parenteral nutrition-related liver disease and intestinal mucosal atrophy in neonatal pigs. Am. J. Physiol. Gastrointest. Liver Physiol. 302:G218–24
    [Google Scholar]
  218. 218. 
    Ehrenkranz RA, Dusick AM, Vohr BR, Wright LL, Wrage LA, Poole WK 2006. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics 117:1253–61
    [Google Scholar]
  219. 219. 
    Ziegler EE, Thureen PJ, Carlson SJ 2002. Aggressive nutrition of the very low birthweight infant. Clin. Perinatol. 29:225–44
    [Google Scholar]
  220. 220. 
    Lee WS, Sokol RJ. 2015. Intestinal microbiota, lipids, and the pathogenesis of intestinal failure-associated liver disease. J. Pediatr. 167:519–26
    [Google Scholar]
  221. 221. 
    Zambrano E, El Hennawy M, Ehrenkranz RA, Zelterman D, Reyes-Mugica M 2004. Total parenteral nutrition induced liver pathology: an autopsy series of 24 newborn cases. Pediatr. Dev. Pathol. 7:425–32
    [Google Scholar]
  222. 222. 
    Duro D, Mitchell PD, Kalish LA, Martin C, McCarthy M et al. 2011. Risk factors for parenteral nutrition-associated liver disease following surgical therapy for necrotizing enterocolitis: a Glaser Pediatric Research Network Study [corrected]. J. Pediatr. Gastroenterol. Nutr. 52:595–600
    [Google Scholar]
  223. 223. 
    Stoll B, Horst DA, Cui L, Chang X, Ellis KJ et al. 2010. Chronic parenteral nutrition induces hepatic inflammation, steatosis, and insulin resistance in neonatal pigs. J. Nutr. 140:2193–200
    [Google Scholar]
  224. 224. 
    Stoll B, Puiman PJ, Cui L, Chang X, Benight NM et al. 2012. Continuous parenteral and enteral nutrition induces metabolic dysfunction in neonatal pigs. J. Parenter. Enter. Nutr. 36:538–50
    [Google Scholar]
  225. 225. 
    Turner JM, Josephson J, Field CJ, Wizzard PR, Ball RO et al. 2015. Liver disease, systemic inflammation, and growth using a mixed parenteral lipid emulsion, containing soybean oil, fish oil, and medium chain triglycerides, compared with soybean oil in parenteral nutrition-fed neonatal pigs. J. Parenter. Enter. Nutr. 40:973–81
    [Google Scholar]
  226. 226. 
    Muto M, Lim D, Soukvilay A, Field C, Wizzard PR et al. 2017. Supplemental parenteral vitamin E into conventional soybean lipid emulsion does not prevent parenteral nutrition-associated liver disease in full-term neonatal pigs. J. Parenter. Enter. Nutr. 41:575–82
    [Google Scholar]
  227. 227. 
    Ng K, Stoll B, Chacko S, Saenz de Pipaon M, Lauridsen C et al. 2016. Vitamin E in new-generation lipid emulsions protects against parenteral nutrition-associated liver disease in parenteral nutrition-fed preterm pigs. J. Parenter. Enter. Nutr. 40:656–71
    [Google Scholar]
  228. 228. 
    Vlaardingerbroek H, Ng K, Stoll B, Benight N, Chacko S et al. 2014. New generation lipid emulsions prevent PNALD in chronic parenterally fed preterm pigs. J. Lipid Res. 55:466–77
    [Google Scholar]
  229. 229. 
    Guthrie G, Kulkarni M, Vlaardingerbroek H, Stoll B, Ng K et al. 2016. Multi-omic profiles of hepatic metabolism in TPN-fed preterm pigs administered new generation lipid emulsions. J. Lipid Res. 57:1696–711
    [Google Scholar]
  230. 230. 
    Lavoie JC, Chessex P. 2019. Parenteral nutrition and oxidant stress in the newborn: a narrative review. Free Radic. Biol. Med. 142:155–67
    [Google Scholar]
  231. 231. 
    El Kasmi KC, Anderson AL, Devereaux MW, Vue PM, Zhang W et al. 2013. Phytosterols promote liver injury and Kupffer cell activation in parenteral nutrition-associated liver disease. Sci. Transl. Med. 5:206ra137
    [Google Scholar]
  232. 232. 
    Koelfat KVK, Schaap FG, Hodin C, Visschers RGJ, Svavarsson BI et al. 2017. Parenteral nutrition dysregulates bile salt homeostasis in a rat model of parenteral nutrition-associated liver disease. Clin. Nutr. 36:1403–10
    [Google Scholar]
  233. 233. 
    Zhan L, Yang I, Kong B, Shen J, Gorczyca L et al. 2016. Dysregulation of bile acid homeostasis in parenteral nutrition mouse model. Am. J. Physiol. Gastrointest. Liver Physiol. 310:G93–G102
    [Google Scholar]
  234. 234. 
    Feng Y, Demehri FR, Xiao W, Tsai YH, Jones JC et al. 2017. Interdependency of EGF and GLP-2 signaling in attenuating mucosal atrophy in a mouse model of parenteral nutrition. Cell. Mol. Gastroenterol. Hepatol. 3:447–68
    [Google Scholar]
  235. 235. 
    Gura KM, Duggan CP, Collier SB, Jennings RW, Folkman J et al. 2006. Reversal of parenteral nutrition-associated liver disease in two infants with short bowel syndrome using parenteral fish oil: implications for future management. Pediatrics 118:e197–e201
    [Google Scholar]
  236. 236. 
    Nandivada P, Fell GL, Gura KM, Puder M 2016. Lipid emulsions in the treatment and prevention of parenteral nutrition-associated liver disease in infants and children. Am. J. Clin. Nutr. 103:629S–34S
    [Google Scholar]
  237. 237. 
    Diamond IR, Grant RC, Pencharz PB, de Silva N, Feldman BM et al. 2016. Preventing the progression of intestinal failure-associated liver disease in infants using a composite lipid emulsion. J. Parenter. Enter. Nutr. 41:866–77
    [Google Scholar]
  238. 238. 
    Repa A, Binder C, Thanhaeuser M, Kreissl A, Pablik E et al. 2018. A mixed lipid emulsion for prevention of parenteral nutrition associated cholestasis in extremely low birth weight infants: a randomized clinical trial. J. Pediatr. 194:87–93.e1
    [Google Scholar]
  239. 239. 
    Molina TL, Stoll B, Mohammad M, Mohila CA, Call L et al. 2019. New generation lipid emulsions increase brain DHA and improve body composition, but not short-term neurodevelopment in parenterally-fed preterm pigs. Brain Behav. Immun In press
    [Google Scholar]
  240. 240. 
    Clayton PT, Bowron A, Mills KA, Massoud A, Casteels M, Milla PJ 1993. Phytosterolemia in children with parenteral nutrition-associated cholestatic liver disease. Gastroenterology 105:1806–13
    [Google Scholar]
  241. 241. 
    Carter BA, Taylor OA, Prendergast DR, Zimmerman TL, Von Furstenberg R et al. 2007. Stigmasterol, a soy lipid-derived phytosterol, is an antagonist of the bile acid nuclear receptor FXR. Pediatr. Res. 62:301–6
    [Google Scholar]
  242. 242. 
    Guthrie G, Tackett B, Stoll B, Martin C, Olutoye O, Burrin DG 2018. Phytosterols synergize with endotoxin to augment inflammation in Kupffer cells but alone have limited direct effect on hepatocytes. J. Parenter. Enter. Nutr. 42:37–48
    [Google Scholar]
  243. 243. 
    El Kasmi KC, Vue PM, Anderson AL, Devereaux MW, Ghosh S et al. 2018. Macrophage-derived IL-1β/NF-κB signaling mediates parenteral nutrition-associated cholestasis. Nat. Commun. 9:1393
    [Google Scholar]
  244. 244. 
    Burrin DG, Ng K, Stoll B, Saenz De Pipaon M 2014. Impact of new-generation lipid emulsions on cellular mechanisms of parenteral nutrition-associated liver disease. Adv. Nutr. 5:82–91
    [Google Scholar]
  245. 245. 
    Teitelbaum DH, Tracy TF Jr, Aouthmany MM, Llanos A, Brown MB et al. 2005. Use of cholecystokinin-octapeptide for the prevention of parenteral nutrition-associated cholestasis. Pediatrics 115:1332–40
    [Google Scholar]
  246. 246. 
    Degirolamo C, Sabba C, Moschetta A 2016. Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23. Nat. Rev. Drug Discov. 15:51–69
    [Google Scholar]
  247. 247. 
    Wright TJ, Ladher R, McWhirter J, Murre C, Schoenwolf GC, Mansour SL 2004. Mouse FGF15 is the ortholog of human and chick FGF19, but is not uniquely required for otic induction. Dev. Biol. 269:264–75
    [Google Scholar]
  248. 248. 
    Inagaki T, Choi M, Moschetta A, Peng L, Cummins CL et al. 2005. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab 2:217–25
    [Google Scholar]
  249. 249. 
    Mudaliar S, Henry RR, Sanyal AJ, Morrow L, Marschall HU et al. 2013. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 145:574–82
    [Google Scholar]
  250. 250. 
    Sánchez-Infantes D, Gallego-Escuredo JM, Díaz M, Aragonés G, Sebastiani G et al. 2015. Circulating FGF19 and FGF21 surge in early infancy from infra- to supra-adult concentrations. Int. J. Obes. 39:742–46
    [Google Scholar]
  251. 251. 
    Memon N, Griffin IJ, Lee CW, Herdt A, Weinberger BI et al. 2018. Developmental regulation of the gut-liver (FGF19-CYP7A1) axis in neonates. J. Matern. Fetal Neonatal Med. In press
    [Google Scholar]
  252. 252. 
    Owen BM, Mangelsdorf DJ, Kliewer SA 2015. Tissue-specific actions of the metabolic hormones FGF15/19 and FGF21. Trends Endocrinol. Metab. 26:22–29
    [Google Scholar]
/content/journals/10.1146/annurev-animal-020518-115142
Loading
/content/journals/10.1146/annurev-animal-020518-115142
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error