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Probiotics and Prebiotics for the Prevention of Necrotizing Enterocolitis

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Abstract

Necrotizing enterocolitis (NEC) continues to be a major cause of morbidity and mortality in premature infants. Although the pathogenesis of NEC remains unclear, abnormal bacterial colonization has been postulated as playing a central role. Various factors impact bacterial colonization following delivery. Compared to term infants, the bacterial colonization pattern in prematurely born infants is markedly different, with a greater predilection for colonization with pathogenic bacteria. Probiotic and prebiotic administration offers the opportunity to manipulate the intestinal bacterial environment, favoring the growth of commensal bacteria. Experimental data from animal studies and data from human trials suggest that probiotics decrease the incidence of NEC. These preliminary studies support the need for a large, randomized, controlled trial to further investigate the role of probiotics in the prevention of NEC.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Henry MC, Moss RL: Necrotizing enterocolitis. Annu Rev Med 2009, 60:111–124.

    Article  CAS  PubMed  Google Scholar 

  2. Thompson AM, Bizzarro MJ: Necrotizing enterocolitis in newborns: pathogenesis, prevention and management. Drugs 2008, 68:1227–1238.

    Article  CAS  PubMed  Google Scholar 

  3. Schnabl KL, Van Aerde JE, Thomson AB, Clandinin MT: Necrotizing enterocolitis: a multifactorial disease with no cure. World J Gastroenterol 2008, 14:2142–2161.

    Article  CAS  PubMed  Google Scholar 

  4. Lin PW, Nasr TR, Stoll BJ: Necrotizing enterocolitis: recent scientific advances in pathophysiology and prevention. Semin Perinatol 2008, 32:70–82.

    Article  PubMed  Google Scholar 

  5. Martin CR, Dammann O, Allred EN, et al.: Neurodevelopment of extremely preterm infants who had necrotizing enterocolitis with or without late bacteremia. J Pediatr 2010, 157:751–756.

    Article  PubMed  Google Scholar 

  6. Santulli TV, Schullinger JN, Heird WC, et al.: Acute necrotizing enterocolitis in infancy: a review of 64 cases. Pediatrics 1975, 55:376–387.

    CAS  PubMed  Google Scholar 

  7. •• Neu J, Douglas-Escobar M, Lopez M: Microbes and the developing gastrointestinal tract. Nutr Clin Pract 2007, 22:174–182. This article provides a thorough review of the microbial colonization in the developing gastrointestinal tract.

    Article  PubMed  Google Scholar 

  8. Mshvildadze M, Neu J, Shuster J, et al.: Intestinal microbial ecology in premature infants assessed with non-culture-based techniques. J Pediatr 2010, 156:20–25.

    Article  PubMed  Google Scholar 

  9. Hentges DJ: Human intestinal microflora in health and disease. 1983, New York: Academic Press.

    Google Scholar 

  10. Morowitz MJ, Poroyko V, Caplan M, et al.: Redefining the role of intestinal microbes in the pathogenesis of necrotizing enterocolitis. Pediatrics 2010, 125:777–785.

    Article  PubMed  Google Scholar 

  11. Biasucci G, Rubini M, Riboni S, et al.: Mode of delivery affects the bacterial community in the newborn gut. Early Hum Dev 2010, 86 Suppl 1:13–15.

    Article  PubMed  Google Scholar 

  12. Morelli L: Postnatal development of intestinal microflora as influenced by infant nutrition. J Nutr 2008, 138:1791S–1795S.

    CAS  PubMed  Google Scholar 

  13. Penders J, Thijs C, Vink C, et al.: Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics 2006, 118:511–521.

    Article  PubMed  Google Scholar 

  14. • Martin CR, Walker WA: Probiotics: role in pathophysiology and prevention in necrotizing enterocolitis. Semin Perinatol 2008, 32:127–137. This article provides a complete review of gut defenses, bacterial colonization, and the use of probiotics for the prevention of NEC.

    Article  PubMed  Google Scholar 

  15. Salminen S, Isolauri E: Opportunities for improving the health and nutrition of the human infant by probiotics. Nestle Nutr Workshop Ser Pediatr Program 2008, 62:223–233; discussion 233–227.

    Article  CAS  PubMed  Google Scholar 

  16. Emami CN, Petrosyan M, Giuliani S, et al.: Role of the host defense system and intestinal microbial flora in the pathogenesis of necrotizing enterocolitis. Surg Infect 2009, 10:407–417.

    Article  Google Scholar 

  17. Sharma R, Tepas JJ 3rd: Microecology, intestinal epithelial barrier and necrotizing enterocolitis. Pediatr Surg Int 2010, 26:11–21.

    Article  PubMed  Google Scholar 

  18. Petrosyan M, Guner YS, Williams M, et al.: Current concepts regarding the pathogenesis of necrotizing enterocolitis. Pediatr Surg Int 2009, 25:309–318.

    Article  PubMed  Google Scholar 

  19. Magne F, Suau A, Pochart P, Desjeux JF: Fecal microbial community in preterm infants. J Pediatr Gastroenterol Nutr 2005, 41:386–392.

    Article  PubMed  Google Scholar 

  20. Mackie RI, Sghir A, Gaskins HR: Developmental microbial ecology of the neonatal gastrointestinal tract. Am J Clin Nutr 1999, 69:1035S–1045S.

    CAS  PubMed  Google Scholar 

  21. Giannone PJ, Nankervis CA, Richter JM, et al.: Prenatal lipopolysaccharide increases postnatal intestinal injury in a rat model of necrotizing enterocolitis. J Pediatr Gastroenterol Nutr 2009, 48:276–282.

    Article  CAS  PubMed  Google Scholar 

  22. Kramer BW, Kallapur SG, Moss TJ, et al.: Modulation of fetal inflammatory response on exposure to lipopolysaccharide by chorioamnion, lung, or gut in sheep. Am J Obstet Gynecol 2010, 202:77 e71–79.

    Article  Google Scholar 

  23. Wolfs TG, Buurman WA, Zoer B, et al.: Endotoxin induced chorioamnionitis prevents intestinal development during gestation in fetal sheep. 2009, PLoS One 4:e5837.

    Article  PubMed  Google Scholar 

  24. Aziz N, Cheng YW, Caughey AB: Neonatal outcomes in the setting of preterm premature rupture of membranes complicated by chorioamnionitis. J Matern Fetal Neonatal Med 2009, 22:780–784.

    PubMed  Google Scholar 

  25. Goldenberg RL, Andrews WW, Faye-Petersen OM, et al.: The Alabama preterm birth study: corticosteroids and neonatal outcomes in 23- to 32-week newborns with various markers of intrauterine infection. Am J Obstet Gynecol 2006, 195:1020–1024.

    Article  CAS  PubMed  Google Scholar 

  26. Kitajima H, Sumida Y, Tanaka R, et al.: Early administration of Bifidobacterium breve to preterm infants: randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 1997, 76:F101–F107.

    Article  CAS  PubMed  Google Scholar 

  27. Agarwal R, Sharma N, Chaudhry R, et al.: Effects of oral Lactobacillus GG on enteric microflora in low-birth-weight neonates. J Pediatr Gastroenterol Nutr 2003, 36:397–402.

    Article  PubMed  Google Scholar 

  28. Manzoni P, Mostert M, Leonessa ML, et al.: Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study. Clin Infect Dis 2006, 42:1735–1742.

    Article  CAS  PubMed  Google Scholar 

  29. Mohan R, Koebnick C, Schildt J, et al.: Effects of Bifidobacterium lactis Bb12 supplementation on intestinal microbiota of preterm infants: a double-blind, placebo-controlled, randomized study. J Clin Microbiol 2006, 44:4025–4031.

    Article  PubMed  Google Scholar 

  30. Rouge C, Piloquet H, Butel MJ, et al.: Oral supplementation with probiotics in very-low-birth-weight preterm infants: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 2009, 89:1828–1835.

    Article  CAS  PubMed  Google Scholar 

  31. Petrof EO, Kojima K, Ropeleski MJ, et al.: Probiotics inhibit nuclear factor-kappaB and induce heat shock proteins in colonic epithelial cells through proteasome inhibition. Gastroenterology 2004, 127:1474–1487.

    Article  CAS  PubMed  Google Scholar 

  32. Claud EC, Lu L, Anton PM, et al.: Developmentally regulated IkappaB expression in intestinal epithelium and susceptibility to flagellin-induced inflammation. Proc Natl Acad Sci U S A 2004, 101:7404–7408.

    Article  CAS  PubMed  Google Scholar 

  33. Korhonen R, Korpela R, Saxelin M, et al.: Induction of nitric oxide synthesis by probiotic Lactobacillus rhamnosus GG in J774 macrophages and human T84 intestinal epithelial cells. Inflammation 2001, 25:223–232.

    Article  CAS  PubMed  Google Scholar 

  34. Otte JM, Podolsky DK: Functional modulation of enterocytes by gram-positive and gram-negative microorganisms. Am J Physiol Gastrointest Liver Physiol 2004, 286:G613–626.

    Article  CAS  PubMed  Google Scholar 

  35. Urao M, Fujimoto T, Lane GJ, et al.: Does probiotics administration decrease serum endotoxin levels in infants? J Pediatr Surg 1999, 34:273–276.

    Article  CAS  PubMed  Google Scholar 

  36. Lin PW, Myers LE, Ray L, et al.: Lactobacillus rhamnosus blocks inflammatory signaling in vivo via reactive oxygen species generation. Free Radic Biol Med 2009, 47:1205–1211.

    Article  CAS  PubMed  Google Scholar 

  37. Lin PW, Nasr TR, Berardinelli AJ, et al.: The probiotic Lactobacillus GG may augment intestinal host defense by regulating apoptosis and promoting cytoprotective responses in the developing murine gut. Pediatr Res 2008, 64:511–516.

    Article  PubMed  Google Scholar 

  38. D’Souza A, Fordjour L, Ahmad A, et al.: Effects of probiotics, prebiotics, and synbiotics on messenger RNA expression of caveolin-1, NOS, and genes regulating oxidative stress in the terminal ileum of formula-fed neonatal rats. Pediatr Res 2010, 67:526–531.

    PubMed  Google Scholar 

  39. Hunter CJ, Williams M, Petrosyan M, et al.: Lactobacillus bulgaricus prevents intestinal epithelial cell injury caused by Enterobacter sakazakii-induced nitric oxide both in vitro and in the newborn rat model of necrotizing enterocolitis. Infect Immun 2009, 77:1031–1043.

    Article  CAS  PubMed  Google Scholar 

  40. Fordjour L, D’Souza A, Cai C, et al.: Comparative effects of probiotics, prebiotics, and synbiotics on growth factors in the large bowel in a rat model of formula-induced bowel inflammation. J Pediatr Gastroenterol Nutr 2010, 51:507–513.

    Article  PubMed  Google Scholar 

  41. Caplan MS, Miller-Catchpole R, Kaup S, et al.: Bifidobacterial supplementation reduces the incidence of necrotizing enterocolitis in a neonatal rat model. Gastroenterology 1999, 117:577–583.

    Article  CAS  PubMed  Google Scholar 

  42. Butel MJ, Roland N, Hibert A, et al.: Clostridial pathogenicity in experimental necrotising enterocolitis in gnotobiotic quails and protective role of bifidobacteria. J Med Microbiol 1998, 47:391–399.

    Article  CAS  PubMed  Google Scholar 

  43. Siggers RH, Siggers J, Boye M, et al.: Early administration of probiotics alters bacterial colonization and limits diet-induced gut dysfunction and severity of necrotizing enterocolitis in preterm pigs. J Nutr 2008, 138:1437–1444.

    CAS  PubMed  Google Scholar 

  44. Khailova L, Dvorak K, Arganbright KM, et al.: Bifidobacterium bifidum improves intestinal integrity in a rat model of necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 2009, 297:G940–949.

    Article  CAS  PubMed  Google Scholar 

  45. Khailova L, Mount Patrick SK, Arganbright KM, et al.: Bifidobacterium bifidum reduces apoptosis in the intestinal epithelium in necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 2010, 299:G1118–1127.

    Google Scholar 

  46. Hoyos AB: Reduced incidence of necrotizing enterocolitis associated with enteral administration of Lactobacillus acidophilus and Bifidobacterium infantis to neonates in an intensive care unit. Int J Infect Dis 1999, 3:197–202.

    Article  CAS  PubMed  Google Scholar 

  47. Lin HC, Su BH, Chen AC, et al.: Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. Pediatrics 2005, 115:1–4.

    Article  PubMed  Google Scholar 

  48. Bin-Nun A, Bromiker R, Wilschanski M, et al.: Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr 2005, 147:192–196.

    Article  PubMed  Google Scholar 

  49. Li LQ, Wu B, Gao XX, et al.: Role of probiotics in the prevention of neonatal necrotizing enterocolitis: A case-control study. Zhongguo Dang Dai Er Ke Za Zhi 2006, 8:464–466.

    PubMed  Google Scholar 

  50. Awad H, Mokhtar H, Imam SS, et al.: Comparison between killed and living probiotic usage versus placebo for the prevention of necrotizing enterocolitis and sepsis in neonates. Pak J Biol Sci 2010, 13:253–262.

    Article  CAS  PubMed  Google Scholar 

  51. Braga TD, da Silva GA, de Lira PI, de Carvalho Lima M. Efficacy of Bifidobacterium breve and Lactobacillus casei oral supplementation on necrotizing enterocolitis in very-low-birth-weight preterm infants: a double-blind, randomized, controlled trial. Am J Clin Nutr 2010 epub Oct 27.

  52. Dani C, Biadaioli R, Bertini G, et al.: Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study. Biol Neonate 2002, 82:103–108.

    Article  CAS  PubMed  Google Scholar 

  53. Luoto R, Matomaki J, Isolauri E, Lehtonen L: Incidence of necrotizing enterocolitis in very-low-birth-weight infants related to the use of Lactobacillus GG. Acta Paediatr 2010, 99:1135–1138.

    Article  CAS  PubMed  Google Scholar 

  54. •• Deshpande G, Rao S, Patole S, Bulsara M: Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics 2010, 125:921–930. This recent meta-analysis for probiotics to prevent NEC includes 11 trials involving 2176 infants.

    Article  PubMed  Google Scholar 

  55. Chou IC, Kuo HT, Chang JS, et al.: Lack of effects of oral probiotics on growth and neurodevelopmental outcomes in preterm very low birth weight infants. J Pediatr 2010, 156:393–396.

    Article  PubMed  Google Scholar 

  56. Gibson GR, Roberfroid MB: Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 1995, 125:1401–1412.

    CAS  PubMed  Google Scholar 

  57. Roberfroid M, Gibson GR, Hoyles L, et al.: Prebiotic effects: metabolic and health benefits. Br J Nutr 2010, 104:S1–S63.

    Article  CAS  PubMed  Google Scholar 

  58. Gnoth MJ, Kunz C, Kinne-Saffran E, Rudloff S: Human milk oligosaccharides are minimally digested in vitro. J Nutr 2000, 130:3014–3020.

    CAS  PubMed  Google Scholar 

  59. Butel MJ, Waligora-Dupriet AJ, Szylit O: Oligofructose and experimental model of neonatal necrotising enterocolitis. Br J Nutr 2002, 87(Suppl 2):S213–S219.

    Article  CAS  PubMed  Google Scholar 

  60. Rao S, Srinivasjois R, Patole S: Prebiotic supplementation in full-term neonates: a systematic review of randomized controlled trials. Arch Pediatr Adolesc Med 2009, 163:755–764.

    Article  PubMed  Google Scholar 

  61. Moro G, Arslanoglu S, Stahl B, et al.: A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age. Arch Dis Child 2006, 91:814–819.

    Article  CAS  PubMed  Google Scholar 

  62. Srinivasjois R, Rao S, Patole S: Prebiotic supplementation of formula in preterm neonates: a systematic review and meta-analysis of randomised controlled trials. Clin Nutr 2009, 28:237–242.

    Article  CAS  PubMed  Google Scholar 

  63. Kapiki A, Costalos C, Oikonomidou C, et al.: The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants. Early Hum Dev 2007, 83:335–339.

    Article  CAS  PubMed  Google Scholar 

  64. Schrezenmeir J, de Vrese M: Probiotics, prebiotics, and synbiotics—approaching a definition. Am J Clin Nutr 2001, 73:361S–364S.

    CAS  PubMed  Google Scholar 

  65. Underwood MA, Salzman NH, Bennett SH, et al.: A randomized placebo-controlled comparison of 2 prebiotic/probiotic combinations in preterm infants: impact on weight gain, intestinal microbiota, and fecal short-chain fatty acids. J Pediatr Gastroenterol Nutr 2009, 48:216–225.

    Article  PubMed  Google Scholar 

  66. Soll RF: Probiotics: are we ready for routine use? Pediatrics 2010, 125:1071–1072.

    Article  PubMed  Google Scholar 

  67. Christensen HR, Frokiaer H, Pestka JJ: Lactobacilli differentially modulate expression of cytokines and maturation surface markers in murine dendritic cells. J Immunol 2002, 168:171–178.

    CAS  PubMed  Google Scholar 

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Disclosure

Conflicts of interest: M. R. Stenger—none; K. M. Reber— stock ownership by children in Procter and Gamble; P. J. Giannone—none; C. A. Nankervis—none.

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Authors and Affiliations

  1. Department of Pediatrics, The Ohio State University College of Medicine and Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH, 43205, USA

    Michael R. Stenger, Kristina M. Reber, Peter J. Giannone & Craig A. Nankervis

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  1. Michael R. Stenger
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  2. Kristina M. Reber
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  3. Peter J. Giannone
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  4. Craig A. Nankervis
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Correspondence to Kristina M. Reber.

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Stenger, M.R., Reber, K.M., Giannone, P.J. et al. Probiotics and Prebiotics for the Prevention of Necrotizing Enterocolitis. Curr Infect Dis Rep 13, 13–20 (2011). https://doi.org/10.1007/s11908-010-0156-6

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