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. 2006 Dec 24;2(4):255–262. doi: 10.1016/S1084-2756(97)80032-2

Role of micro-organisms in necrotizing enterocolitis

David CA Candy 1,1, Seán P Devane 1
PMCID: PMC7129339  PMID: 32288484

Abstract

The frequency with which necrotizing enterocolitis occurs in outbreaks makes it likely that the illness can have an infective origin. Immunological and non-immunological defences of the gastrointestinal are impaired in early life. Consequently the gut of the preterm infant is predisposed to bacterial overgrowth. A wide range of pathogenic bacteria and viruses have been isolated from infants with necrotizing enterocolitis or detected histologically. The presence of bacterial metabolites in the breath, intestinal bullae (hydrogen) and urine (D-lactate) during the course of the illness is further confirmatory evidence. The presence of bacteria or bacterial products (such as exo- and endotoxin) in the circulation will lead to ischaemia of the intestine and other organs either directly or via mediators such as cytokines or platelet activating factor. Future studies in necrotizing enterocolitis should be directed to understanding and modulating inflammatory mediators in necrotizing enterocolitis and preventing the disease with breast milk and nutritional supplements (glutamine, short chain fatty acids), chemoprophylaxis, and antibodies.

Key words: necrotizing enterocolitis, intestinal flora, bacterial overgrowth, endotoxin, tumour necrosis factor, interleukins, intestinal ischaemia

References

  • 1.Pedersen PV, Hansen FH, Halveg AB, Christiansen ED. Necrotising enterocolitis of the newborn: is it gasgangrene of the bowel? Lancet. 1976;ii:715–716. doi: 10.1016/s0140-6736(76)90009-x. [DOI] [PubMed] [Google Scholar]
  • 2.Kosloske AM, Ulrick JA, Hoffman H. Fulminant necrotising enterocolitis associated with Clostridia. Lancet. 1978;ii:1014–1016. doi: 10.1016/s0140-6736(78)92337-1. [DOI] [PubMed] [Google Scholar]
  • 3.Howard FM, Flynn DM, Bradley JM. Outbreak of necrotising enterocolitis caused by Clostridium butyricum. Lancet. 1977;ii:1099–1102. doi: 10.1016/s0140-6736(77)90546-3. [DOI] [PubMed] [Google Scholar]
  • 4.Blakey JL, Lubitz L, Barnes GL. Development of gut colonization in preterm neonates. J Med Microbiol. 1982;15:519–529. doi: 10.1099/00222615-15-4-519. [DOI] [PubMed] [Google Scholar]
  • 5.Westra-Meijer CMM, Degener JE, Dzoljic-Danilovic G. Quantitative study of the aerobic and anaerobic faecal flora in neonatal necrotising enterocolitis. Arch Dis Child. 1983;58:523–528. doi: 10.1136/adc.58.7.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Grand RJ, Watkins JB, Torti FM. Development of the human gastrointestinal tract. Gastroenterology. 1976;70:790–810. [PubMed] [Google Scholar]
  • 7.Bisset WM, Watt J, Rivers RPA, Milla PJ. The ontogeny of fasting small intestinal motor activity in the human infant. Gut. 1988;29:483–488. doi: 10.1136/gut.29.4.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Kolacek S, Puntis JWL, Lloyd DR. Ontogeny of pancreatic exocrine function. Arch Dis Child. 1990;65:178–181. doi: 10.1136/adc.65.2.178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Rozee KR, Cooper D, Lam K, Costerton JW. Microbial flora of the mouse ileum mucous layer and epithelial surface. Appl Environ Microbiol. 1982;43:1451–1463. doi: 10.1128/aem.43.6.1451-1463.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Souba WW, Herskowitz K, Salloum RM. Gut glutamine metabolism. J Parent Ent Nutr. 1990;14:45–50S. doi: 10.1177/014860719001400403. (suppl) [DOI] [PubMed] [Google Scholar]
  • 11.Alexander JW. Nutrition and translocation. J Parent Ent Nutr. 1990;14:170–174S. doi: 10.1177/014860719001400505. (suppl) [DOI] [PubMed] [Google Scholar]
  • 12.Perkio M, Savilahti E. Time of appearance of immunoglobulin-containing cells in the mucosa of the neonatal intestine. Pediatr Res. 1980;14:953–955. doi: 10.1203/00006450-198008000-00012. [DOI] [PubMed] [Google Scholar]
  • 13.Burgio GR, Lanzavecchia A, Plebani A. Ontogeny of secretory immunity: levels of secretory IgA and natural antibodies in saliva. Pediatr Res. 1980;14:1111–1114. doi: 10.1203/00006450-198010000-00004. [DOI] [PubMed] [Google Scholar]
  • 14.Guy-Grand D, Griscelli C, Vassalli P. The mouse gut T lymphocyte, a novel type of T cell: nature, origin and traffic in mice in normal and graft-versus-host conditions. J Exp Med. 1978;148:1661–1677. doi: 10.1084/jem.148.6.1661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Anon Surveillance of necrotising enterocolitis 1981–2. Brit Med J. 1983;287:824–826. doi: 10.1136/bmj.287.6395.824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Clark DA, Thompson JE, Weiner LB. Necrotizing enterocolitis: intraluminal biochemistry in human neonates and a rabbit model. Pediatr Res. 1985;19:919–921. doi: 10.1203/00006450-198509000-00010. [DOI] [PubMed] [Google Scholar]
  • 17.Eibl M, Wolf H, Furnkranz H, Rosenkrantz A. Prevention of necrotizing enterocolitis in low birth weight infants by IgA-IgG feeding. New Engl J Med. 1988;319:1–7. doi: 10.1056/NEJM198807073190101. [DOI] [PubMed] [Google Scholar]
  • 18.Rubaltelli FF, Benini F, Sala M. Prevention of necrotising enterocolitis in neonates at risk by oral administration of monomeric IgG. Dev Pharmacol Ther. 1991;17:138–143. doi: 10.1159/000457513. [DOI] [PubMed] [Google Scholar]
  • 19.Ng PC, Dear PRF, Thomas DFM. Oral vancomycin in prevention of necrotising enterocolitis. Arch Dis Childh. 1988;63:1390–1393. doi: 10.1136/adc.63.11.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Cheu HW, Brown DR, Rowe MI. Breath hydrogen excretion as a screening test for early diagnosis of necrotizing enterocolitis. Am J Dis Child. 1989;143:156–159. doi: 10.1001/archpedi.1989.02150140042017. [DOI] [PubMed] [Google Scholar]
  • 21.Garcia J, Smith FR, Cucinell SA. Urinary D-lactate excretion in infants with necrotizing enterocolitis. J Pediatr. 1984;104:268–270. doi: 10.1016/s0022-3476(84)81010-0. [DOI] [PubMed] [Google Scholar]
  • 22.Barlow B, Santulli TV. Importance of multiple episodes of hypoxia or cold stress on the development of enterocolitis in an animal model. Surg. 1975;77:687–690. [PubMed] [Google Scholar]
  • 23.Caplan M, Sun X-M, Hsueh W, Hageman JR. Role of platelet activating factor and tumour necrosis factor-alpha in neonatal necrotising enterocolitis. J Pediatr. 1990;116:961–964. doi: 10.1016/s0022-3476(05)80661-4. [DOI] [PubMed] [Google Scholar]
  • 24.Hsueh W, Gonzalez-Crussi F, Arroyave JL. Release of leukotriene C4 by isolated, perfused rat small intestine in response to platelet-activating factor. J Clin Invest. 1986;78:108–114. doi: 10.1172/JCI112538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Cueva JP, Hsueh W. Role of oxygen-derived free radicals in platelet activating factor induced bowel necrosis. Gut. 1988;29:1207–1212. doi: 10.1136/gut.29.9.1207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Ballance WA, Dahms BB, Shenker N, Kliegman RM. Pathology of neonatal necrotising enterocolitis: a ten-year experience. J Pediatr. 1990;117(1):S6–S13. doi: 10.1016/s0022-3476(05)81124-2. pt 2. [DOI] [PubMed] [Google Scholar]
  • 27.Mitchell TJ, Ketley JM, Haslam SC. The effect of toxin A and B of Clostridium difficile on rabbit ileum and colon. Gut. 1986;27:78–85. doi: 10.1136/gut.27.1.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Molby R, Aronsson B, Nord CE. Pathogenesis and diagnosis of Clostridium difficile enterocolitis. Scand J Infect Dis Suppl. 1985;46:47–56. [PubMed] [Google Scholar]
  • 29.Cushing AH. Necrotizing enterocolitis with Escherichia coli heat-labile enterotoxin. Pediatr. 1983;71:626–630. [PubMed] [Google Scholar]
  • 30.Scheifele DW, Bjornson GL, Dyer RA. Delta-like toxin produced by coagulase-negative staphylococci is associated with neonatal necrotizing enterocolitis. Infect Immun. 1987;55:2268–2273. doi: 10.1128/iai.55.9.2268-2273.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Osborne MP, Haddon SJ, Worton KJ. A study of the microcirculation in whole villi of neonatal mice using a peroxidase histochemical staining method. J Pediatr Gastroenterol. 1991;12:105–110. doi: 10.1097/00005176-199101000-00020. [DOI] [PubMed] [Google Scholar]
  • 32.Osborne MP, Haddon SJ, Worton KJ. Rotavirus-induced changes in the microcirculation of intestinal villi of neonatal mice in relation to the induction and persistence of diarrhea. J Pediatr Gastroenterol. 1991;12:111–120. doi: 10.1097/00005176-199101000-00021. [DOI] [PubMed] [Google Scholar]
  • 33.Scheifele DW, Olsen E, Fussel S, Pendray M. Spontaneous endotoxinemia in premature infants: correlations with oral feeding and bowel dysfunction. J Pediatr Gastroenterol Nutr. 1985;4:67–74. doi: 10.1097/00005176-198502000-00013. [DOI] [PubMed] [Google Scholar]
  • 34.Starnes HF, Pearce MK, Tewari A. Anti-IL-6 monoclonal antibodies protect against lethal Escherichia coli infection and lethal tumour necrosis factor-alpha challenge in mice. J Immunol. 1990;145:4185–4191. [PubMed] [Google Scholar]
  • 35.Camussi G, Bussolino F, Salvidio G, Baglioni C. Tumor necrosis factor cachectin stimulates peritoneal macrophages, polymorphonuclear neutrophils, and vascular endothelial cells to synthesize and release platelet activating factor. J Exper Med. 1987;166:1390–1404. doi: 10.1084/jem.166.5.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.de Silva DGH, Mendis LN, Sheron N. Concentrations of interleukin-6 and tumour necrosis factor in serum and stools of children with Shigella dysenteriae 1 infection. Gut. 1993;34:194–198. doi: 10.1136/gut.34.2.194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Millar MR, MacKay P, Levene M. Enterobacteriaceae and neonatal necrotising enterocolitis. Arch Dis Child. 1992;67:53–56. doi: 10.1136/adc.67.1_spec_no.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Lucas A, Cole TJ. Breast milk and neonatal necrotising enterocolitis. Lancet. 1990;336:1519–1523. doi: 10.1016/0140-6736(90)93304-8. [DOI] [PubMed] [Google Scholar]
  • 39.Sun X, Hsueh W. Bowel necrosis induced by tumor necrosis factor in rats is mediated by platelet-activaing factor. J Clin Invest. 1988;81:1328–1333. doi: 10.1172/JCI113459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Kliegman RM, Fanaroff AA. Necrotizing enterocolitis. N Engl J Med. 1984;310:1093–1103. doi: 10.1056/NEJM198404263101707. [DOI] [PubMed] [Google Scholar]

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