Necrotizing Enterocolitis: Probiotics, Prebiotics and Synbiotics for Prevention in Preterm Infants
Keywords:
Necrotizing Enterocolitis, Toll-like receptors, Probiotics, Prebiotics
Abstract
Necrotizing enterocolitis is a devastating disease of newborns associated with intestinal inflammation and necrosis. In spite of advances in neonatal care, intensive care units and refinement of surgical practices, the high mortality and long term morbidity due to NEC remains a challenge. The pathogenesis of the disease is complicated and not completely understood. Gradual development in the field of NEC revealed innate immune system, comprised of ‘Toll-like receptors’ (TLR) in the pathogenesis of the disease. TLR4 is an important member of TLR and is the receptor for bacterial lipopolysaccharide. Activation of TLR4 causes intestinal mucosal injury and decreased epithelial repair in premature neonates. Probiotics are live microorganisms and are rich in bacterial DNA. CpG motifs of DNA can inhibit TLR4 signaling and reduce NEC severity. Probiotics also modulate enterocyte genes that regulate innate immune-mediated inflammation, thereby preventing NEC. The above molecular basis is supported by multiple individual studies using probiotics especially Lactobacillus and Bifidobacteria for preventing NEC in preterm infants. Their encouraging results prompted us to carry out an analysis of major trials on probiotics along with considering pathophysiological and immunological aspects of the disease.
Prebiotics have a protective effect in NEC by stimulating colonization of beneficial bacteria in intestine. Products containing both probiotics and prebiotics (synbiotics) were also tried and they are found to be more beneficial than either probiotics or prebiotics. This review will highlight recent concepts and evidences on probiotics and prebiotics in preventing NEC in preterm, low birth weight infants.
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References
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8. Qasem W Alnaqi A, Jorgensen S, Friel J. Probiotic and Synbiotics in Necrotizing Enterocolitis: Where Are We? J Pediatr Neonatal Care 2014; 1(1): 00007. DOI: 10.15406/jpnc.2014.01.00007.
9. Frost BL, Caplan MS. Necrotizing Enterocolitis: Pathophysiology, platelet-activating factor, and probiotics. Semin Pediatr Surg. 2013May;22(2):88-93. doi: 10.1053/j.sempedsurg.2013.01.005.
10. Heather J.L. Brooks, Michelle A. McConnell and Roland S. Broadbent (2013). Microbes and the Inflammatory Response in Necrotising Enterocolitis, Preterm Birth, Dr. Offer Erez (Ed.), InTech, DOI: 10.5772/55039. Available from: http://www.intechopen.com/books/preterm-birth/microbes-and-the-inflammatory-response-in-necrotising-enterocolitis
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12. Tripathy PK, Nanda R. Management Modalities for Necrotizing Enterocolitis: Targeting Toll-Like Receptors. AABS. 2016; 3(1): R1-R5. e-ISSN: 2349-6991; p-ISSN: 2455-0396.
13. Afrazi A, S Sodhi CP, Richardson W, Neal M, Good M, Siggers R, Hackam D. New Insights Into the Pathogenesis and Treatment of Necrotizing Enterocolitis: Toll- Like Receptors and Beyond. Pediatric Research. 2011Mar; 69(3): 183-8. DOI: 10.1203/PDR.0b013e3182093280.
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15. Hackam DJ, Afrazi A, Good M, Sodhi CP. Innate Immune Signaling in the Pathogenesis of Necrotizing Enterocolitis. Clin Dev Immunol. 2013;2013:475415. DOI: 10.1155/2013/475415. Epub 2013 May 23. [PubMed]
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17. Mack DR, Michail S, Wei S, McDougall L, Hollingsworth MA. Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression. Am J Physiol. 1999 April;276(4 Pt 1): G941-G950. [PubMed]
18. Hunter CJ, Upperman JS, Ford HR, Camerini V. Understanding the susceptibility of the premature infant in Necrotizing Enterocolitis(NEC). Pediatr Res 2008; 63:117-123. DOI:10.1203/PDR.0b013e31815ed64c. [PubMed]
19. Caballero-FrancoC, KellerK, De Simonne C, Chadee K. The VSL#3 probiotic formula induces mucin gene expression and secretion in colonic epithelial cells. AM J Physiol Gastrointest Liver. January2007; 292:G315-G322 doi:10.1152/ajpgi.00265.2006.
20. Hoyos AB. Reduced incidence of necrotizing enterocolitis associated with enteral administration of Lactobacillus acidophilus and Bifidobacterium infantis to neonates in the intensive care unit. Int J Infect Dis. 1999; 3(4): 197-202.
21. Bin-Nun A, Bromiker R, Wilschanski M, Kaplan M, Rudensky B, Caplan M, Hammerman C. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr. 2005 Aug;147(2):192-196. DOI:10.1016/j.jpeds.2005.03.054. [PubMed]
22. Lin HC, Su BH, Chen AC, Lin TW, Tsai CH, Yeh TF, Oh W. Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. Pediatrics. 2005;115(1):1-4. DOI:10.1542/peds.2004-1463. [PubMed]
23. Lin HC, Hsu CH, Chen HL, Chung MY, Hsu JF, Lien RI, et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicentre, randomized, controlled trial. Pediatrics 2008;122: 693-700. doi: 10.1542/peds.2007-3007.
24. Samanta M, Sarkar M, Ghosh P, Ghosh JK, Sinha MK, Chatterjee S. Prophlactic probiotics for prevention of necrotizing enterocolitis in very low birth weight newborns. J Trop Pediatr.2009Apr, 55(2) :128-131. DOI: 10.1093/tropej/fmn091. Epub 2008 Oct 8. [PubMed]
25. Rouge C, Piloquet H, Butel MJ, Berger B, Rochat Fllorence, Ferraris L, 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(6) ;1828-35. doi: 10.3945/ajcn.2008.26919. Epub 2009 Apr 15.
26. Dani C, Biadaioli R, Bertini G, Martelli E, Rubaltelli FF. 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.DOI:10.1159/000063096.
27. Sari FN, Dizdar FA, Oguz S, Erdeve O, Uras N, Dilmen U. Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: A randomized, controlled trial. Eur J Clin Nutr. 2011 Apr;65(4):434-439. doi: 10.1038/ejcn.2010.278. Epub 2011 Jan 19.
28. Manzoni P, Rinaldi M, Cattani S, Pugni L, Romeo MG, Messner H, Stolfi I, et al. Decembrino L, Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low birth neonates: A randomized trial. JAMA. 2009 Oct 7;302(13):1421-8. doi: 10.1001/jama.2009.1403.
29. Mazoni P, Lista G, Gallo E, Marangione P, Priolo C, Fontana P, Guardione R, Farina D. Routine lactobacillus rhamnosus GG administration in VLWL infants. Early Hum Dev. 2011 Mar; 87 Suppl 1:S35-8. doi: 10.1016/j.earlhumdev.2011.01.036. Epub 2011 Feb 3. [PubMed]
30. Deshpande G, Rao S, Patole S, Bulsara M. Updated Meta-analysis of Probiotics for Preventing Necrotizing Enterocolitis in Preterm Neonates. Pediatrics. 2010 May;125(5):921-30. doi: 10.1542/peds.2009-1301. Epub 2010 Apr 19. [PubMed]
31. AlFaleh K, Anabrees J. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev. 2014 Apr 10;(4):CD005496. doi: 10.1002/14651858.CD005496.pub4.
32. 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. 2011 Jan; 93(1):81-86. doi: 10.3945/ajcn.2010.29799. Epub 2010 Oct 27.
33. Wang Q, Dong J, Zhu Y. Probiotic supplement reduces risk of necrotizing enterocolitis and mortality in preterm very-low-birth-weight infants; an updated meta-analysis of 20 randomized controlled trials. J Pediatr Surg. 2012 Jan;47(1):241-8. doi: 10.1016/j.jpedsurg.2011.09.064.
34. Bernado WM, Aires FT, Carneiro RM, Sa FP, Rullo VE, Burns DA. Effectiveness of probiotics in the prophylaxis of necrotizing enterocolitis in preterm neonates: a systematic review and meta-analysis. J Pediatr ( Rio J). 2013;89:18-24.http://dx.doi.org/10.1016/j.jped.2013.02.004.
35. Bandopadhyay B, Mandal NC, Probiotic, Prebiotics and Synbiotics – In Health Improvement by Modulating Gut Microbiota : The Concept Revisited. Int J Curr Microbiol App Sci.2014; 3(3): 410-420.
36. Caplan MS. Probiotic and prebiotic supplementation for prevention of neonatal necrotizing enterocolitis. J Perinatol. 2009 May;29 Suppl 2:S2-6. doi: 10.1038/jp.2009.21.
37. Boehm G, Lidestri M, Casetta P, et al. Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of fecal bifidobacteria in preterm infants. Archives of Disease in Childhood.2002;86(3):F178–F181.
38. Mihatsch W, Hoegel J, Pohlandt F. Prebiotic oligosaccharides reduce stool viscosity and accelerate gastrointestinal transport in preterm infants. Acta Paediatrica. 2006;95(7):843–848.
39. Indrio F, Riezzo G, Montagna O, Valenzano E, Mautone A, Boehm G. Effect of a prebiotic mixture of short chain galacto-oligosaccharides and long chain fructo-oligosaccharides on gastric motility in preterm infants. Journal of Pediatric Gastroenterology and Nutrition. 2007;(article e122).
40. Kapiki A, Costalos C, Oikonomidou C, Triantafyllidou A, Loukatou E, Pertrohilou V. The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants. Early Human Development.2007;83(5):335–339. pub 2006 Sep 14.
41. Sylvester KG, Liu GY, Albanese CT. Necrotizing Enterocolitis. In Coran AG, Adzick NS, Krummel TM, Laberge J, Shamberger RC, Caldamone AA. Pediatric Surgery. 7th Edn. Philadelphia: Elsevier Saunders, 2012. Chapter 94, p 1187-1207.
42. Bury RG, Tudehope D. Enteral antibiotics for preventing necrotizing enterocolitis in low birth weight or preterm infants. Cochrane Database Syst Rev. 2001;(1):CD000405. DOI: 10.1002/14651858.CD000405.
2. Sari FN, Dilmen U. Probiotic Use for Prevention of Necrotizing Enterocolitis in Preterm Infants.(c) 2012 Sari and Dilmen, licensee InTech. http://dx.doi.org/10.5772/50049. Downloaded from http://www.intechopen.com/download/pdf/39601
3. Kriston G, Meng Di, Rautava S, Lu L, Walker WA, Nanthakumar N. Probiotics prevent necrotizing enterocolitis by modulating enterocyte genes that regulate innate immune –mediated inflammation. Am J Physiol Gastrointest Liver Physiol.2013 Jan 15. 304(2); G132-G141. DOI: 10.1152/ajpgi.00142.2012.
4. Ganguli K, Meng D, Rautava S, Lu L, Walker WA, Nanthakumar N. Probiotics prevent necrotizing enterocolitis by modulating enterocyte genes that regulate innate immune-mediated inflammation. Am J Physiol Gastrointest Liver Physiol. 2013 Jan 15;304(2):G132-41. doi: 10.1152/ajpgi.00142.2012. Epub 2012 Nov 8.
5. Patel B, Shah JS. Necrotozing Enterocolitis in Very Low Birth Weight Infants: A Systematic Review. ISRN Gastroenterol. 2012; 2012:562594. Published online 2012 Sep 10. DOI: 10.5402/2012/562594. [PubMed]
6. Chen CC, Walker A. Probiotics and the mechanism of necrotizing enterocolitis. Seminars in Pediatric Surgery.2013; 22:94-100. doi: 10.1053/j.sempedsurg.2013.01.006. [PubMed]
7. Johnson-Henry KC, Abrahamsson TR, Wu RY, Sherman PM. Probiotics, Prebiotics and Synbiotics for the Prevention of Necrotizing Enterocolitis. Adv Nutr. 2016 Sep 15;7(5):928-37. doi: 10.3945/an.116.012237. Review.PMID:27633108.
8. Qasem W Alnaqi A, Jorgensen S, Friel J. Probiotic and Synbiotics in Necrotizing Enterocolitis: Where Are We? J Pediatr Neonatal Care 2014; 1(1): 00007. DOI: 10.15406/jpnc.2014.01.00007.
9. Frost BL, Caplan MS. Necrotizing Enterocolitis: Pathophysiology, platelet-activating factor, and probiotics. Semin Pediatr Surg. 2013May;22(2):88-93. doi: 10.1053/j.sempedsurg.2013.01.005.
10. Heather J.L. Brooks, Michelle A. McConnell and Roland S. Broadbent (2013). Microbes and the Inflammatory Response in Necrotising Enterocolitis, Preterm Birth, Dr. Offer Erez (Ed.), InTech, DOI: 10.5772/55039. Available from: http://www.intechopen.com/books/preterm-birth/microbes-and-the-inflammatory-response-in-necrotising-enterocolitis
11. Niekerk V. Probiotics in premature infants: focus on necrotizing enterocolitis. S Afr J CLin Nutr. 2011; 24(3):S35-S37. Access from http://www.ajol.info/index.php/sajcn/article/viewFile/69809/57892
12. Tripathy PK, Nanda R. Management Modalities for Necrotizing Enterocolitis: Targeting Toll-Like Receptors. AABS. 2016; 3(1): R1-R5. e-ISSN: 2349-6991; p-ISSN: 2455-0396.
13. Afrazi A, S Sodhi CP, Richardson W, Neal M, Good M, Siggers R, Hackam D. New Insights Into the Pathogenesis and Treatment of Necrotizing Enterocolitis: Toll- Like Receptors and Beyond. Pediatric Research. 2011Mar; 69(3): 183-8. DOI: 10.1203/PDR.0b013e3182093280.
14. De Curtis M, Terrin G. Necrotizing enterocolitis(NEC) what’s going on. Journal of Pediatric and Neonatal Individualized Medicine 2013;2(2):e020218 doi: 10.7363/020218 Advance publication: 2013 Aug 21.
15. Hackam DJ, Afrazi A, Good M, Sodhi CP. Innate Immune Signaling in the Pathogenesis of Necrotizing Enterocolitis. Clin Dev Immunol. 2013;2013:475415. DOI: 10.1155/2013/475415. Epub 2013 May 23. [PubMed]
16. Soll RF. Probiotics: are we ready for routine use? Pediatrics 2010:125:1071-1072. doi: 10.1542/peds.2010-0643. pmid: 20421256 Epub 2010 Apr 26. [PubMed]
17. Mack DR, Michail S, Wei S, McDougall L, Hollingsworth MA. Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression. Am J Physiol. 1999 April;276(4 Pt 1): G941-G950. [PubMed]
18. Hunter CJ, Upperman JS, Ford HR, Camerini V. Understanding the susceptibility of the premature infant in Necrotizing Enterocolitis(NEC). Pediatr Res 2008; 63:117-123. DOI:10.1203/PDR.0b013e31815ed64c. [PubMed]
19. Caballero-FrancoC, KellerK, De Simonne C, Chadee K. The VSL#3 probiotic formula induces mucin gene expression and secretion in colonic epithelial cells. AM J Physiol Gastrointest Liver. January2007; 292:G315-G322 doi:10.1152/ajpgi.00265.2006.
20. Hoyos AB. Reduced incidence of necrotizing enterocolitis associated with enteral administration of Lactobacillus acidophilus and Bifidobacterium infantis to neonates in the intensive care unit. Int J Infect Dis. 1999; 3(4): 197-202.
21. Bin-Nun A, Bromiker R, Wilschanski M, Kaplan M, Rudensky B, Caplan M, Hammerman C. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr. 2005 Aug;147(2):192-196. DOI:10.1016/j.jpeds.2005.03.054. [PubMed]
22. Lin HC, Su BH, Chen AC, Lin TW, Tsai CH, Yeh TF, Oh W. Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. Pediatrics. 2005;115(1):1-4. DOI:10.1542/peds.2004-1463. [PubMed]
23. Lin HC, Hsu CH, Chen HL, Chung MY, Hsu JF, Lien RI, et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicentre, randomized, controlled trial. Pediatrics 2008;122: 693-700. doi: 10.1542/peds.2007-3007.
24. Samanta M, Sarkar M, Ghosh P, Ghosh JK, Sinha MK, Chatterjee S. Prophlactic probiotics for prevention of necrotizing enterocolitis in very low birth weight newborns. J Trop Pediatr.2009Apr, 55(2) :128-131. DOI: 10.1093/tropej/fmn091. Epub 2008 Oct 8. [PubMed]
25. Rouge C, Piloquet H, Butel MJ, Berger B, Rochat Fllorence, Ferraris L, 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(6) ;1828-35. doi: 10.3945/ajcn.2008.26919. Epub 2009 Apr 15.
26. Dani C, Biadaioli R, Bertini G, Martelli E, Rubaltelli FF. 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.DOI:10.1159/000063096.
27. Sari FN, Dizdar FA, Oguz S, Erdeve O, Uras N, Dilmen U. Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: A randomized, controlled trial. Eur J Clin Nutr. 2011 Apr;65(4):434-439. doi: 10.1038/ejcn.2010.278. Epub 2011 Jan 19.
28. Manzoni P, Rinaldi M, Cattani S, Pugni L, Romeo MG, Messner H, Stolfi I, et al. Decembrino L, Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low birth neonates: A randomized trial. JAMA. 2009 Oct 7;302(13):1421-8. doi: 10.1001/jama.2009.1403.
29. Mazoni P, Lista G, Gallo E, Marangione P, Priolo C, Fontana P, Guardione R, Farina D. Routine lactobacillus rhamnosus GG administration in VLWL infants. Early Hum Dev. 2011 Mar; 87 Suppl 1:S35-8. doi: 10.1016/j.earlhumdev.2011.01.036. Epub 2011 Feb 3. [PubMed]
30. Deshpande G, Rao S, Patole S, Bulsara M. Updated Meta-analysis of Probiotics for Preventing Necrotizing Enterocolitis in Preterm Neonates. Pediatrics. 2010 May;125(5):921-30. doi: 10.1542/peds.2009-1301. Epub 2010 Apr 19. [PubMed]
31. AlFaleh K, Anabrees J. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev. 2014 Apr 10;(4):CD005496. doi: 10.1002/14651858.CD005496.pub4.
32. 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. 2011 Jan; 93(1):81-86. doi: 10.3945/ajcn.2010.29799. Epub 2010 Oct 27.
33. Wang Q, Dong J, Zhu Y. Probiotic supplement reduces risk of necrotizing enterocolitis and mortality in preterm very-low-birth-weight infants; an updated meta-analysis of 20 randomized controlled trials. J Pediatr Surg. 2012 Jan;47(1):241-8. doi: 10.1016/j.jpedsurg.2011.09.064.
34. Bernado WM, Aires FT, Carneiro RM, Sa FP, Rullo VE, Burns DA. Effectiveness of probiotics in the prophylaxis of necrotizing enterocolitis in preterm neonates: a systematic review and meta-analysis. J Pediatr ( Rio J). 2013;89:18-24.http://dx.doi.org/10.1016/j.jped.2013.02.004.
35. Bandopadhyay B, Mandal NC, Probiotic, Prebiotics and Synbiotics – In Health Improvement by Modulating Gut Microbiota : The Concept Revisited. Int J Curr Microbiol App Sci.2014; 3(3): 410-420.
36. Caplan MS. Probiotic and prebiotic supplementation for prevention of neonatal necrotizing enterocolitis. J Perinatol. 2009 May;29 Suppl 2:S2-6. doi: 10.1038/jp.2009.21.
37. Boehm G, Lidestri M, Casetta P, et al. Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of fecal bifidobacteria in preterm infants. Archives of Disease in Childhood.2002;86(3):F178–F181.
38. Mihatsch W, Hoegel J, Pohlandt F. Prebiotic oligosaccharides reduce stool viscosity and accelerate gastrointestinal transport in preterm infants. Acta Paediatrica. 2006;95(7):843–848.
39. Indrio F, Riezzo G, Montagna O, Valenzano E, Mautone A, Boehm G. Effect of a prebiotic mixture of short chain galacto-oligosaccharides and long chain fructo-oligosaccharides on gastric motility in preterm infants. Journal of Pediatric Gastroenterology and Nutrition. 2007;(article e122).
40. Kapiki A, Costalos C, Oikonomidou C, Triantafyllidou A, Loukatou E, Pertrohilou V. The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants. Early Human Development.2007;83(5):335–339. pub 2006 Sep 14.
41. Sylvester KG, Liu GY, Albanese CT. Necrotizing Enterocolitis. In Coran AG, Adzick NS, Krummel TM, Laberge J, Shamberger RC, Caldamone AA. Pediatric Surgery. 7th Edn. Philadelphia: Elsevier Saunders, 2012. Chapter 94, p 1187-1207.
42. Bury RG, Tudehope D. Enteral antibiotics for preventing necrotizing enterocolitis in low birth weight or preterm infants. Cochrane Database Syst Rev. 2001;(1):CD000405. DOI: 10.1002/14651858.CD000405.
CITATION
DOI: 10.17511/ijpr.2016.i11.15
Published: 2016-11-30
How to Cite
Dr Prasanta Kumar Tripathy, & Dr Rachita Nanda. (2016). Necrotizing Enterocolitis: Probiotics, Prebiotics and Synbiotics for Prevention in Preterm Infants. Pediatric Review: International Journal of Pediatric Research, 3(11), 856-865. https://doi.org/10.17511/ijpr.2016.i11.15
Section
Review Article
Copyright (c) 2016 Author (s). Published by Siddharth Health Research and Social Welfare Society
This work is licensed under a Creative Commons Attribution 4.0 International License.
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