Evolving understanding of neonatal necrotizing enterocolitis

Current Opinion in Pediatrics

Volumn 30, Issue 3, 2018, Pages 417-423

  Isani, Mubina A ^a   Delaplain, Patrick T ^a   Grishin, Anatoly ^a   Ford, Henri R ^a,b  

^a CHILDREN S HOSPITAL LOS ANGELES   (United States)

^b UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

growth factors; microbiota; necrotizing enterocolitis; pathogenesis; premature

Indexed keywords

GROWTH FACTOR; PROBIOTIC AGENT;

BREAST FEEDING; HUMAN; IMMUNOCOMPETENT CELL; INTESTINE CELL; MICROBIOME; NECROTIZING ENTEROCOLITIS; NEWBORN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; INTESTINE FLORA; PREMATURITY; RISK FACTOR;

BREAST FEEDING; ENTEROCOLITIS, NECROTIZING; GASTROINTESTINAL MICROBIOME; HUMANS; INFANT, NEWBORN; INFANT, PREMATURE; INFANT, PREMATURE, DISEASES; PROBIOTICS; RISK FACTORS;

EID: 85048095693     PISSN: 10408703     EISSN: 1531698X     Source Type: Journal    
DOI: 10.1097/MOP.0000000000000629     Document Type: Review

References (108)

1. Hodzic Z, Bolock AM, Good M. The role of mucosal immunity in the pathogenesis of necrotizing enterocolitis. Front Pediatr 2017; 5:40
2. Holman RC, Stoll BJ, Curns AT, et al. Necrotising enterocolitis hospitalisations among neonates in the United States. Paediatr Perinat Epidemiol 2006; 20:498-506
3. Fitzgibbons SC, Ching Y, Yu D, et al. Mortality of necrotizing enterocolitis expressed by birth weight categories. J Pediatr Surg 2009; 44:1072-1075; discussion 5-6
4. Bisquera JA, Cooper TR, Berseth CL. Impact of necrotizing enterocolitis on length of stay and hospital charges in very low birth weight infants. Pediatrics 2002; 109:423-428
5. Stey A, Barnert ES, Tseng CH, et al. Outcomes and costs of surgical treatments of necrotizing enterocolitis. Pediatrics 2015; 135:e1190-e1197
6. Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med 2011; 364: 255-264
7. Neu J. Necrotizing enterocolitis: the mystery goes on. Neonatology 2014; 106:289-295
8. Nino DF, Sodhi CP, Hackam DJ. Necrotizing enterocolitis: new insights into pathogenesis and mechanisms. Nat Rev Gastroenterol Hepatol 2016; 13:590-600
9. Sharma R, HudakML. A clinical perspective of necrotizing enterocolitis: past, present, and future. Clin Perinatol 2013; 40:27-51
10. Cobb BA, Carlo WA, Ambalavanan N. Gastric residuals and their relationship to necrotizing enterocolitis in very low birth weight infants. Pediatrics 2004; 113(1 Pt 1):50-53
11. Torrazza RM, Parker LA, Li Y, et al. The value of routine evaluation of gastric residuals in very low birth weight infants. J Perinatol 2015; 35:57-60
12. Sylvester KG, Ling XB, Liu GY, et al. A novel urine peptide biomarker-based algorithm for the prognosis of necrotising enterocolitis in human infants. Gut 2014; 63:1284-1292
13. Sylvester KG, Ling XB, Liu GY, et al. Urine protein biomarkers for the diagnosis and prognosis of necrotizing enterocolitis in infants. J Pediatr 2014; 164:607-612.e1-7
14. Bell MJ, Ternberg JL, Feigin RD, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978; 187:1-7
15. Rehan VK, Seshia MM, Johnston B, et al. Observer variability in interpretation of abdominal radiographs of infants with suspected necrotizing enterocolitis. Clin Pediatr (Phila) 1999; 38:637-643
16. McBride WJ, Roy S, Brudnicki A, Stringel G. Correlation of complex ascites with intestinal gangrene and perforation in neonates with necrotizing enterocolitis. J Pediatr Surg 2010; 45:887-889
17. Yikilmaz A, Hall NJ, Daneman A, et al. Prospective evaluation of the impact of sonography on the management and surgical intervention of neonates with necrotizing enterocolitis. Pediatr Surg Int 2014; 30:1231-1240
18. Maalouf EF, Fagbemi A, Duggan PJ, et al. Magnetic resonance imaging of intestinal necrosis in preterm infants. Pediatrics 2000; 105(3 Pt 1): 510-514
19. Moore JE. Newer monitoring techniques to determine the risk of necrotizing enterocolitis. Clin Perinatol 2013; 40:125-134
20. Maheshwari A, Schelonka RL, Dimmitt RA, et al. Cytokines associated with necrotizing enterocolitis in extremely-low-birth-weight infants. Pediatr Res 2014; 76:100-108
21. Ng PC. Biomarkers of necrotising enterocolitis. Semin Fetal Neonatal Med 2014; 19:33-38
22. Niemarkt HJ, de Meij TG, van de Velde ME, et al. Necrotizing enterocolitis: a clinical review on diagnostic biomarkers and the role of the intestinal microbiota. Inflamm Bowel Dis 2015; 21:436-444
23. Schurink M, Kooi EM, Hulzebos CV, et al. Intestinal fatty acid-binding protein as a diagnostic marker for complicated and uncomplicated necrotizing enterocolitis: a prospective cohort study. PLoS One 2015; 10:e0121336
24. Heida FH, Hulscher JB, Schurink M, et al. Intestinal fatty acid-binding protein levels in necrotizing enterocolitis correlate with extent of necrotic bowel: results from a multicenter study. J Pediatr Surg 2015; 50:1115-1118
25. Touloukian RJ, Berdon WE, Amoury RA, Santulli TV. Surgical experience with necrotizing enterocolitis in the infant. J Pediatr Surg 1967; 2:389-401
26. Zani A, Eaton S, Puri P, et al. International survey on the management of necrotizing enterocolitis. Eur J Pediatr Surg 2015; 25:27-33
27. Guthrie SO, Gordon PV, Thomas V, et al. Necrotizing enterocolitis among neonates in the United States. J Perinatol 2003; 23:278-285
28. Muller A, Schurink M, Bos AF, et al. Clinical importance of a fixed bowel loop in the treatment of necrotizing enterocolitis. Neonatology 2014; 105:33-38
29. Neu J, Pammi M. Pathogenesis of NEC: impact of an altered intestinal microbiome. Semin Perinatol 2017; 41:29-35
30. Santaolalla R, Abreu MT. Innate immunity in the small intestine. Curr Opin Gastroenterol 2012; 28:124-129
31. van der Flier LG, Clevers H. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol 2009; 71:241-260
32. Hunter CJ, Singamsetty VK, Chokshi NK, et al. Enterobacter sakazakii enhances epithelial cell injury by inducing apoptosis in a rat model of necrotizing enterocolitis. J Infect Dis 2008; 198:586-593
33. Nadler EP, Dickinson E, Knisely A, et al. Expression of inducible nitric oxide synthase and interleukin-12 in experimental necrotizing enterocolitis. J Surg Res 2000; 92:71-77
34. 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
35. Short SS, Wang J, Castle SL, et al. Low doses of celecoxib attenuate gut barrier failure during experimental peritonitis. Lab Invest 2013; 93: 1265-1275
36. Lugo B, Ford HR, Grishin A. Molecular signaling in necrotizing enterocolitis: regulation of intestinal COX-2 expression. J Pediatr Surg 2007; 42: 1165-1171
37. Papillon S, Castle SL, Gayer CP, Ford HR. Necrotizing enterocolitis: contemporary management and outcomes. Adv Pediatr 2013; 60:263-279
38. Lim JC, Golden JM, Ford HR. Pathogenesis of neonatal necrotizing enterocolitis. Pediatr Surg Int 2015; 31:509-518
39. Grishin A, Bowling J, Bell B, et al. Roles of nitric oxide and intestinal microbiota in the pathogenesis of necrotizing enterocolitis. J Pediatr Surg 2016; 51:13-17
40. Vitale S, Picascia S, Gianfrani C. The cross-talk between enterocytes and intraepithelial lymphocytes. Mol Cell Pediatr 2016; 3:20
41. Snoeck V, Goddeeris B, Cox E. The role of enterocytes in the intestinal barrier function and antigen uptake. Microbes Infect 2005; 7:997-1004
42. Vereecke L, Beyaert R, van Loo G. Enterocyte death and intestinal barrier maintenance in homeostasis and disease. Trends Mol Med 2011; 17: 584-593
43. Miron N, Cristea V. Enterocytes: active cells in tolerance to food and microbial antigens in the gut. Clin Exp Immunol 2012; 167:405-412
44. Abreu MT. Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function. Nat Rev Immunol 2010; 10:131-144
45. Hershberg RM, Mayer LF. Antigen processing and presentation by intestinal epithelial cells-polarity and complexity. Immunol Today 2000; 21: 123-128
46. Hershberg RM, Framson PE, Cho DH, et al. Intestinal epithelial cells use two distinct pathways for HLA class II antigen processing. J Clin Invest 1997; 100:204-215
47. Tanner SM, Berryhill TF, Ellenburg JL, et al. Pathogenesis of necrotizing enterocolitis: modeling the innate immune response. Am J Pathol 2015; 185:4-16
48. Sodhi CP, Neal MD, Siggers R, et al. Intestinal epithelial Toll-like receptor 4 regulates goblet cell development and is required for necrotizing enterocolitis in mice. Gastroenterology 2012; 143:708-718. e5
49. Johansson ME, Larsson JM, Hansson GC. The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions. Proc Natl Acad Sci U S A 2011; 108(Suppl 1): 4659-4665
50. Clark JA, Lane RH, Maclennan NK, et al. Epidermal growth factor reduces intestinal apoptosis in an experimental model of necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 2005; 288:G755-G762
51. Clark JA, Doelle SM, Halpern MD, et al. Intestinal barrier failure during experimental necrotizing enterocolitis: protective effect of EGF treatment. Am J Physiol Gastrointest Liver Physiol 2006; 291:G938-G949
52. Bevins CL, Salzman NH. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol 2011; 9:356-368
53. Salzman NH, Hung K, Haribhai D, et al. Enteric defensins are essential regulators of intestinal microbial ecology. Nat Immunol 2010; 11: 76-83
54. Biswas A, Liu YJ, Hao L, et al. Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum. Proc Natl Acad Sci U S A 2010; 107:14739-14744
55. McElroy SJ, Underwood MA, Sherman MP. Paneth cells and necrotizing enterocolitis: a novel hypothesis for disease pathogenesis. Neonatology 2013; 103:10-20
56. Sato A. Tuft cells. Anat Sci Int 2007; 82:187-199
57. Gribble FM, Reimann F. Enteroendocrine cells: chemosensors in the intestinal epithelium. Annu Rev Physiol 2016; 78:277-299
58. Worthington JJ. The intestinal immunoendocrine axis: novel cross-talk between enteroendocrine cells and the immune system during infection and inflammatory disease. Biochem Soc Trans 2015; 43:727-733
59. Palazzo M, Balsari A, Rossini A, et al. Activation of enteroendocrine cells via TLRs induces hormone, chemokine, and defensin secretion. J Immunol 2007; 178:4296-4303
60. Cani PD, Everard A, Duparc T. Gut microbiota, enteroendocrine functions and metabolism. Curr Opin Pharmacol 2013; 13:935-940
61. McElroy SJ, Weitkamp JH. Innate immunity in the small intestine of the preterm infant. Neoreviews 2011; 12:e517-e526
62. Mombaerts P, Iacomini J, Johnson RS, et al. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 1992; 68:869-877
63. Egan CE, Sodhi CP, Good M, et al. Toll-like receptor 4-mediated lymphocyte influx induces neonatal necrotizing enterocolitis. J Clin Invest 2016; 126:495-508
64. Maheshwari A, Kelly DR, Nicola T, et al. TGF-b2 suppresses macrophage cytokine production and mucosal inflammatory responses in the developing intestine. Gastroenterology 2011; 140:242-253
65. Emami CN, Mittal R, Wang L, et al. Recruitment of dendritic cells is responsible for intestinal epithelial damage in the pathogenesis of necrotizing enterocolitis by Cronobacter sakazakii. J Immunol 2011; 186: 7067-7079
66. Emami CN, Mittal R, Wang L, et al. Role of neutrophils and macrophages in the pathogenesis of necrotizing enterocolitis caused by Cronobacter sakazakii. J Surg Res 2012; 172:18-28
67. Cong Y, Feng T, Fujihashi K, et al. A dominant, coordinated T regulatory cell-IgA response to the intestinal microbiota. Proc Natl Acad Sci U S A 2009; 106:19256-19261
68. Borges MC, Sesso ML, Roberti LR, et al. Salivary antibody response to streptococci in preterm and fullterm children: a prospective study. Arch Oral Biol 2015; 60:116-125
69. Nogueira RD, Sesso ML, Borges MC, et al. Salivary IgA antibody responses to Streptococcus mitis and Streptococcus mutans in preterm and fullterm newborn children. Arch Oral Biol 2012; 57:647-653
70. Lu P, Sodhi CP, Hackam DJ. Toll-like receptor regulation of intestinal development and inflammation in the pathogenesis of necrotizing enterocolitis. Pathophysiology 2014; 21:81-93
71. Neal MD, Leaphart C, Levy R, et al. Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinal barrier. J Immunol 2006; 176:3070-3079
72. Liu Y, Zhu L, Fatheree NY, et al. Changes in intestinal Toll-like receptors and cytokines precede histological injury in a rat model of necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 2009; 297:G442-G450
73. Ninõ DF, Sodhi CP, Egan CE, et al. Retinoic acid improves incidence and severity of necrotizing enterocolitis by lymphocyte balance restitution and repopulation of LGR5 intestinal stem cells. Shock 2017; 47:22-32
74. Afrazi A, Branca MF, Sodhi CP, et al. Toll-like receptor 4-mediated endoplasmic reticulum stress in intestinal crypts induces necrotizing enterocolitis. J Biol Chem 2014; 289:9584-9599
75. Pammi M, Cope J, Tarr PI, et al. Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis. Microbiome 2017; 5:31
76. Barron LK, Warner BB, Tarr PI, et al. Independence of gut bacterial content and neonatal necrotizing enterocolitis severity. J Pediatr Surg 2017; 52: 993-998
77. Peter CS, Feuerhahn M, Bohnhorst B, et al. Necrotising enterocolitis: is there a relationship to specific pathogens? Eur J Pediatr 1999; 158:67-70
78. Dvorak K, Coursodon-Boyiddle CF, Snarrenberg CL, et al. Helicobacter hepaticus increases intestinal injury in a rat model of necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 2013; 305:G585-G592
79. 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
80. Kanto WP Jr, Hunter JE, Stoll BJ. Recognition and medical management of necrotizing enterocolitis. Clin Perinatol 1994; 21:335-346
81. Warner BB, Deych E, Zhou Y, et al. Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study. Lancet 2016; 387:1928-1936
82. Rusconi B, Good M, Warner BB. The microbiome and biomarkers for necrotizing enterocolitis: are we any closer to prediction? J Pediatr 2017; 189:40-47. e2
83. Warner BB, Tarr PI. Necrotizing enterocolitis and preterm infant gut bacteria. Semin Fetal Neonatal Med 2016; 21:394-399
84. Rees CM, Eaton S, Kiely EM, et al. Peritoneal drainage or laparotomy for neonatal bowel perforation? A randomized controlled trial. Ann Surg 2008; 248:44-51
85. Loftin CD, Tiano HF, Langenbach R. Phenotypes of the COX-deficient mice indicate physiological and pathophysiological roles for COX-1 and COX-2. Prostaglandins Other Lipid Mediat 2002; 68-69:177-185
86. Wang D, Dubois RN. The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene 2010; 29:781-788
87. Grishin AV, Wang J, Potoka DA, et al. Lipopolysaccharide induces cyclooxygenase-2 in intestinal epithelium via a noncanonical p38 MAPK pathway. J Immunol 2006; 176:580-588
88. Cuna A, Sampath V. Genetic alterations in necrotizing enterocolitis. Semin Perinatol 2017; 41:61-69
89. Sampath V, Menden H, Helbling D, et al. SIGIRR genetic variants in premature infants with necrotizing enterocolitis. Pediatrics 2015; 135: e1530-e1534
90. Sampath V, Le M, Lane L, et al. The NFKB1 (g.-24519delATTG) variant is associated with necrotizing enterocolitis (NEC) in premature infants. J Surg Res 2011; 169:e51-e57
91. Sampath V, Bhandari V, Berger J, et al. A functional ATG16L1 (T300A) variant is associated with necrotizing enterocolitis in premature infants. Pediatr Res 2017; 81:582-588
92. Good M, Sodhi CP, Hackam DJ. Evidence-based feeding strategies before and after the development of necrotizing enterocolitis. Expert Rev Clin Immunol 2014; 10:875-884
93. Lönnerdal B. Bioactive proteins in human milk: mechanisms of action. J Pediatr 2010; 156(2 Suppl):S26-S30
94. Warner BB, Ryan AL, Seeger K, et al. Ontogeny of salivary epidermal growth factor and necrotizing enterocolitis. J Pediatr 2007; 150:358-363
95. Warner BW, Warner BB. Role of epidermal growth factor in the pathogenesis of neonatal necrotizing enterocolitis. Semin Pediatr Surg 2005; 14: 175-180
96. Coursodon CF, Dvorak B. Epidermal growth factor and necrotizing enterocolitis. Curr Opin Pediatr 2012; 24:160-164
97. Singh AB, Harris RC. Epidermal growth factor receptor activation differentially regulates claudin expression and enhances transepithelial resistance in Madin-Darby canine kidney cells. J Biol Chem 2004; 279:3543-3552
98. Taylor JA, Bernabe KQ, Guo J, Warner BW. Epidermal growth factor receptor-directed enterocyte proliferation does not induce Wnt pathway transcription. J Pediatr Surg 2007; 42:981-986
99. Maynard AA, Dvorak K, Khailova L, et al. Epidermal growth factor reduces autophagy in intestinal epithelium and in the rat model of necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 2010; 299: G614-G622
100. Helmrath MA, Shin CE, Fox JW, et al. Adaptation after small bowel resection is attenuated by sialoadenectomy: the role for endogenous epidermal growth factor. Surgery 1998; 124:848-854
101. Helmrath MA, Shin CE, Erwin CR, Warner BW. Intestinal adaptation is enhanced by epidermal growth factor independent of increased ileal epidermal growth factor receptor expression. J Pediatr Surg 1998; 33: 980-984; discussion 4-5
102. He Y, Schmidt MA, Erwin C, et al. Transgenic soybean production of bioactive human epidermal growth factor (EGF). PLoS One 2016; 11: e0157034
103. Isani M, Illingworth L, Herman E, et al. Soybean-derived recombinant human epidermal growth factor protects against experimental necrotizing enterocolitis. J Pediatr Surg 2018. (In press). https://doi. org/10. 1016/j. jpedsurg. 2018. 02. 084
104. Xia G, Lara-Marquez M, Luquette MH, et al. Heparin-binding EGF-like growth factor decreases inducible nitric oxide synthase and nitric oxide production after intestinal ischemia/reperfusion injury. Antioxid Redox Signal 2001; 3:919-930
105. Yang J, Su Y, Zhou Y, Besner GE. Heparin-binding EGF-like growth factor (HB-EGF) therapy for intestinal injury: application and future prospects. Pathophysiology 2014; 21:95-104
106. Radulescu A, Zhang HY, Yu X, et al. Heparin-binding epidermal growth factor-like growth factor overexpression in transgenic mice increases resistance to necrotizing enterocolitis. J Pediatr Surg 2010; 45:1933-1939
107. Sawh SC, Deshpande S, Jansen S, et al. Prevention of necrotizing enterocolitis with probiotics: a systematic review and meta-analysis. PeerJ 2016; 4:e2429
108. Costeloe K, Bowler U, Brocklehurst P, et al. A randomised controlled trial of the probiotic Bifidobacterium breve BBG-001 in preterm babies to prevent sepsis, necrotising enterocolitis and death: the Probiotics in Preterm infantS (PiPS) trial. Health Technol Assess 2016; 20:1-194