Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 11/2019

01-11-2019 | Probiotics | Review

Recent Advances in Prevention and Therapies for Clinical or Experimental Necrotizing Enterocolitis

Authors: Kewei Wang, Guozhong Tao, Karl G. Sylvester

Published in: Digestive Diseases and Sciences | Issue 11/2019

Login to get access

Abstract

Necrotizing enterocolitis (NEC) is one of the most severe diseases of preterm neonates and has a high mortality rate. With the development of inspection techniques and new biomarkers, the diagnostic accuracy of NEC is constantly improving. The most recognized potential risk factors include prematurity, formula-feeding, infection, and microbial dysbiosis. With further understanding of the pathogenesis, more effective prevention and therapies will be applied to clinical or experimental NEC. At present, such new potential prevention and therapies for NEC are mainly focused on the Toll-like receptor 4 inflammatory signaling pathway, the repair of intestinal barrier function, probiotics, antioxidative stress, breast-feeding, and immunomodulatory agents. Many new studies have changed our understanding of the pathogenesis of NEC and improve our approaches for preventing and treating of NEC each year. This review provides an overview of the recent researches focused on clinical or experimental NEC and highlights the advances made within the past 5 years toward the development of new potential preventive approaches and therapies for this disease.
Literature
1.
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 1075–1076.PubMed
2.
McElroy SJ. Unraveling the enigma that is neonatal necrotizing enterocolitis. J Perinatol. 2014;34:729–730.PubMed
3.
Sankaran K, Puckett B, Lee DS, et al. Variations in incidence of necrotizing enterocolitis in Canadian neonatal intensive care units. J Pediatr Gastroenterol Nutr. 2004;39:366–372.PubMed
4.
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.PubMedPubMedCentral
5.
Berkhout D, Klaassen P, Niemarkt HJ, et al. Risk factors for necrotizing enterocolitis: a prospective multicenter case-control study. Neonatology. 2018;114:277–284.PubMed
6.
Neu J, Pammi M. Pathogenesis of NEC: impact of an altered intestinal microbiome. Semin Perinatol. 2017;41:29–35.PubMed
7.
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.PubMedPubMedCentral
8.
Elgin TG, Kern SL, McElroy SJ. Development of the neonatal intestinal microbiome and its association with necrotizing enterocolitis. Clin Ther. 2016;38:706–715.PubMed
9.
10.
Sharma R, Hudak ML. A clinical perspective of necrotizing enterocolitis: past, present, and future. Clin Perinatol. 2013;40:27–51.PubMedPubMedCentral
11.
Hunter CJ, De Plaen IG. Inflammatory signaling in NEC: role of NF-κB, cytokines and other inflammatory mediators. Pathophysiology. 2014;21:55–65.PubMed
12.
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.PubMed
13.
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.PubMed
14.
Hackam DJ, Sodhi CP, Good M. New insights into necrotizing enterocolitis: from laboratory observation to personalized prevention and treatment. J Pediatr Surg. 2019;54:398–404.PubMed
15.
Zhou Y, Li Y, Zhou B, et al. Inflammation and apoptosis: dual mediator role for toll-like receptor 4 in the development of necrotizing enterocolitis. Inflamm Bowel Dis. 2017;23:44–56.PubMed
16.
Huang K, Mukherjee S, DesMarais V, et al. Targeting the PXR-TLR4 signaling pathway to reduce intestinal inflammation in an experimental model of necrotizing enterocolitis. Pediatr Res. 2018;83:1031–1040.PubMedPubMedCentral
17.
Hou Y, Lu X, Zhang Y. IRAK inhibitor protects the intestinal tract of necrotizing enterocolitis by inhibiting the toll-like receptor (TLR) inflammatory signaling pathway in rats. Med Sci Monit. 2018;24:3366–3373.PubMedPubMedCentral
18.
Tian F, Liu GR, Li N, Yuan G. Insulin-like growth factor I reduces the occurrence of necrotizing enterocolitis by reducing inflammatory response and protecting intestinal mucosal barrier in neonatal rats model. Eur Rev Med Pharmacol Sci. 2017;21:4711–4719.PubMed
19.
Shi Y, Liu T, Zhao X, et al. Vitamin D ameliorates neonatal necrotizing enterocolitis via suppressing TLR4 in a murine model. Pediatr Res. 2018;83:1024–1030.PubMed
20.
Qi W, Shen Q, Zhang L, Han LP, Wang S. Study on the inflammatory intervention of erythropoietin on NEC. Exp Ther Med. 2016;11:2221–2224.PubMedPubMedCentral
21.
Wipf P, Eyer BR, Yamaguchi Y, et al. Synthesis of anti-inflammatory α-and β-linked acetamidopyranosides as inhibitors of toll-like receptor 4 (TLR4). Tetrahedron Lett. 2015;56:3097–3100.PubMedPubMedCentral
22.
Bein A, Eventov-Friedman S, Arbell D, Schwartz B. Intestinal tight junctions are severely altered in NEC preterm neonates. Pediatr Neonatol. 2018;59:464–473.PubMed
23.
Halpern MD, Denning PW. The role of intestinal epithelial barrier function in the development of NEC. Tissue Barriers. 2015;3:e1000707.PubMedPubMedCentral
24.
Grothaus JS, Ares G, Yuan C, Wood DR, Hunter CJ. Rho kinase inhibition maintains intestinal and vascular barrier function by upregulation of occludin in experimental necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol. 2018;315:G514–G528.PubMedPubMedCentral
25.
Xiao S, Li Q, Hu K, et al. Vitamin A and retinoic acid exhibit protective effects on necrotizing enterocolitis by regulating intestinal flora and enhancing the intestinal epithelial barrier. Arch Med Res. 2018;49:1–9.PubMed
26.
Denkel LA, Schwab F, Garten L, Geffers C, Gastmeier P, Piening B. Dual-strain probiotics reduce NEC, mortality and neonatal bloodstream infections among extremely low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 2017;102:F559–F560.PubMed
27.
Denkel LA, Schwab F, Garten L, Geffers C, Gastmeier P, Piening B. Protective effect of dual-strain probiotics in preterm infants: a multi-center time series analysis. PLoS ONE. 2016;11:e0158136.PubMedPubMedCentral
28.
Wu W, Wang Y, Zou J, et al. Bifidobacterium adolescentis protects against necrotizing enterocolitis and upregulates TOLLIP and SIGIRR in premature neonatal rats. BMC Pediatr. 2017;17:1.PubMedPubMedCentral
29.
Ling X, Linglong P, Weixia D, Hong W. Protective effects of bifidobacterium on intestinal barrier function in LPS-induced enterocyte barrier injury of Caco-2 monolayers and in a rat NEC model. PLoS ONE. 2016;11:e0161635.PubMedPubMedCentral
30.
Zhu XL, Tang XG, Qu F, Zheng Y, Zhang WH, Diao YQ. Bifidobacterium may benefit the prevention of necrotizing enterocolitis in preterm infants: a systematic review and meta-analysis. Int J Surg. 2019;61:17–25.PubMed
31.
Olson JK, Navarro JB, Allen JM, et al. An enhanced Lactobacillus reuteri biofilm formulation that increases protection against experimental necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol. 2018;315:G408–G419.PubMedPubMedCentral
32.
Fleming P, Hall NJ, Eaton S. Probiotics and necrotizing enterocolitis. Pediatr Surg Int. 2015;31:1111–1118.PubMed
33.
Olson JK, Rager TM, Navarro JB, Mashburn-Warren L, Goodman SD, Besner GE. Harvesting the benefits of biofilms: a novel probiotic delivery system for the prevention of necrotizing enterocolitis. J Pediatr Surg. 2016;51:936–941.PubMed
34.
Singh B, Shah PS, Afifi J, et al. Probiotics for preterm infants: a national retrospective cohort study. J Perinatol. 2019;28:1.
35.
Floch MH, Walker WA, Sanders ME, et al. Recommendations for probiotic use–2015 update: proceedings and consensus opinion. J Clin Gastroenterol. 2015;49:S69–73.PubMed
36.
Underwood MA. Probiotics and the prevention of necrotizing enterocolitis. J Pediatr Surg. 2019;54:405–412.PubMed
37.
Kane AF, Bhatia AD, Denning PW, Shane AL, Patel RM. Routine supplementation of Lactobacillus rhamnosus GG and risk of necrotizing enterocolitis in very low birth weight infants. J Pediatr. 2018;195:e2.
38.
Perrone S, Tataranno ML, Santacroce A, Negro S, Buonocore G. The role of oxidative stress on necrotizing enterocolitis in very low birth weight infants. Curr Pediatr Rev. 2014;10:202–207.PubMed
39.
Buyuktiryaki M, Tayman C, Koyuncu I, et al. Therapeutic and preventative effects of ankaferd blood stopper in an experimental necrotizing enterocolitis model. Biomed Pharmacother. 2019;110:105–110.PubMed
40.
Yazıcı S, Ozcan CU, Hismiogullari AA, et al. Protective effects of quercetin on necrotizing enterocolitis in a neonatal rat model. Am J Perinatol. 2018;35:434–440.PubMed
41.
Cigsar EB, Ali Karadag C, Tanik C, Fatih Aydin A, Ihsan Dokucu A. The protective effects of sesamol in a neonatal rat model of necrotizing enterocolitis. J Matern Fetal Neonatal Med. 2018;2018:1–6.
42.
Cakir U, Tayman C, Serkant U, et al. Ginger (Zingiber officinale Roscoe) for the treatment and prevention of necrotizing enterocolitis. J Ethnopharmacol. 2018;225:297–308.PubMed
43.
44.
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.PubMed
45.
Li X, Li X, Shang Q, et al. Fecal microbiota transplantation (FMT) could reverse the severity of experimental necrotizing enterocolitis (NEC) via oxidative stress modulation. Free Radic Biol Med. 2017;108:32–43.PubMed
46.
Cacho NT, Parker LA, Neu J. Necrotizing enterocolitis and human milk feeding: a systematic review. Clin Perinatol. 2017;44:49–67.PubMed
47.
Aceti A, Beghetti I, Martini S, Faldella G, Corvaglia L. Oxidative stress and necrotizing enterocolitis: pathogenetic mechanisms, opportunities for intervention, and role of human milk. Oxid Med Cell Longev. 2018;2018:7397659.PubMedPubMedCentral
48.
Chowning R, Radmacher P, Lewis S, Serke L, Pettit N, Adamkin DH. A retrospective analysis of the effect of human milk on prevention of necrotizing enterocolitis and postnatal growth. J Perinatol. 2016;36:221–224.PubMed
49.
Autran CA, Kellman BP, Kim JH, et al. Human milk oligosaccharide composition predicts risk of necrotising enterocolitis in preterm infants. Gut. 2018;67:1064–1070.PubMed
50.
Armanian AM, Sadeghnia A, Hoseinzadeh M, et al. The effect of neutral oligosaccharides on reducing the incidence of necrotizing enterocolitis in preterm infants: a randomized clinical trial. Int J Prev Med. 2014;5:1387–1395.PubMedPubMedCentral
51.
Isani MA, Delaplain PT, Grishin A, Ford HR. Evolving understanding of neonatal necrotizing enterocolitis. Curr Opin Pediatr. 2018;30:417–423.PubMed
52.
Good M, Sodhi CP, Egan CE, et al. Breast milk protects against the development of necrotizing enterocolitis through inhibition of Toll-like receptor 4 in the intestinal epithelium via activation of the epidermal growth factor receptor. Mucosal Immunol. 2015;8:1166–1179.PubMedPubMedCentral
53.
Isani M, Illingworth L, Herman E, et al. Soybean-derived recombinant human epidermal growth factor protects against experimental necrotizing enterocolitis. J Pediatr Surg. 2018;53:1203–1207.PubMed
54.
Pammi M, Suresh G. Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev. 2017;6:CD007137.PubMed
55.
Pammi M, Abrams SA. Oral lactoferrin for the prevention of sepsis and necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev. 2015;2015:CD007137.
56.
Akin IM, Atasay B, Dogu F, et al. Oral lactoferrin to prevent nosocomial sepsis and necrotizing enterocolitis of premature neonates and effect on T-regulatory cells. Am J Perinatol. 2014;31:1111–1120.PubMed
57.
He Y, Cao L, Yu J. Prophylactic lactoferrin for preventing late-onset sepsis and necrotizing enterocolitis in preterm infants: a PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2018;97:e11976.
58.
Manzoni P, Meyer M, Stolfi I, et al. Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial. Early Hum Dev. 2014;90:S60–65.PubMed
59.
Shen RL, Thymann T, Østergaard MV, et al. 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. 2015;309:G310–323.PubMed
60.
Li B, Hock A, Wu RY, et al. Bovine milk-derived exosomes enhance goblet cell activity and prevent the development of experimental necrotizing enterocolitis. PLoS ONE. 2019;14:e0211431.PubMedPubMedCentral
61.
Matheson PJ, Walker SK, Maki AC, Shaheen SP, Neal Garrison R, Downard CD. Oral relaxin maintains intestinal blood flow in a rat model of NEC. J Pediatr Surg. 2014;49:961–964; discussion 964–965.PubMed
62.
McElroy SJ, Castle SL, Bernard JK, et al. The ErbB4 ligand neuregulin-4 protects against experimental necrotizing enterocolitis. Am J Pathol. 2014;184:2768–2778.PubMedPubMedCentral
63.
Maheshwari A. Immunologic and hematological abnormalities in necrotizing enterocolitis. Clin Perinatol. 2015;42:567–585.PubMedPubMedCentral
64.
Feng Z, Zhou H, Ma S, et al. FTY720 attenuates intestinal injury and suppresses inflammation in experimental necrotizing enterocolitis via modulating CXCL5/CXCR64 axis. Biochem Biophys Res Commun. 2018;505:1032–1037.PubMed
65.
Zhou P, Li Y, Ma LY, Lin HC. The role of immunonutrients in the prevention of necrotizing enterocolitis in preterm very low birth weight infants. Nutrients. 2015;7:7256–7270.PubMedPubMedCentral
66.
Garg BD, Kabra NS. Role of amino acid supplementation in the prevention of necrotizing enterocolitis in preterm neonates—a review of current evidences. J Matern Fetal Neonatal Med. 2018;31:2349–2366.PubMed
67.
Shah PS, Shah VS, LE Kelly. Arginine supplementation for prevention of necrotising enterocolitis in preterm infants. Cochrane Database Syst Rev. 2017;4:CD004339.PubMed
68.
El-Shimi MS, Awad HA, Abdelwahed MA, Mohamed MH, Khafagy SM, Saleh G. Enteral l-arginine and glutamine supplementation for prevention of NEC in preterm neonates. Int J Pediatr. 2015;2015:856091.PubMedPubMedCentral
69.
Zani A, Cananzi M, Fascetti-Leon F, et al. Amniotic fluid stem cells improve survival and enhance repair of damaged intestine in necrotising enterocolitis via a COX-2 dependent mechanism. Gut. 2014;63:300–309.PubMed
70.
Wei J, Zhou Y, Besner GE. Heparin-binding EGF-like growth factor and enteric neural stem cell transplantation in the prevention of experimental necrotizing enterocolitis in mice. Pediatr Res. 2015;78:29–37.PubMedPubMedCentral
71.
Bowker RM, Yan X, Managlia E, et al. Dimethyloxalylglycine preserves the intestinal microvasculature and protects against intestinal injury in a neonatal mouse NEC model: role of VEGF signaling. Pediatr Res. 2018;83:545–553.PubMed
72.
Corsini I, Polvani S, Tarocchi M, et al. Peroxisome proliferator-activated receptor-γ agonist pioglitazone reduces the development of necrotizing enterocolitis in a neonatal preterm rat model. Pediatr Res. 2017;81:364–368.PubMed
73.
Klinke M, Vincent D, Trochimiuk M, et al. Degradation of extracellular DNA significantly ameliorates necrotizing enterocolitis severity in mice. J Surg Res. 2019;235:513–520.PubMed
74.
Yin Y, Qin Z, Xu X, et al. Inhibition of miR-124 improves neonatal necrotizing enterocolitis via an MYPT1 and TLR9 signal regulation mechanism. J Cell Physiol. 2019;234:10218–10224.PubMed
75.
Blackwood BP, Wood DR, Yuan C, et al. A role for cAMP and protein kinase a in experimental necrotizing enterocolitis. Am J Pathol. 2017;187:401–417.PubMedPubMedCentral
76.
Al-Wassia H, Shah PS. Efficacy and safety of umbilical cord milking at birth: a systematic review and meta-analysis. JAMA Pediatr. 2015;169:18–25.PubMed
77.
Sekhon MK, Yoder BA. Impact of umbilical cord milking and pasteurized donor human milk on necrotizing enterocolitis: a retrospective review. BMC Pediatr. 2018;18:155.PubMedPubMedCentral
Metadata
Title
Recent Advances in Prevention and Therapies for Clinical or Experimental Necrotizing Enterocolitis
Authors
Kewei Wang
Guozhong Tao
Karl G. Sylvester
Publication date
01-11-2019
Publisher
Springer US
Keyword
Probiotics
Published in
Digestive Diseases and Sciences / Issue 11/2019
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-019-05618-2

Other articles of this Issue 11/2019

Digestive Diseases and Sciences 11/2019 Go to the issue

Concise Commentary

Concise Commentary: Pocketing the Difference—Genetics and the Changing Paradigms of Diverticulitis Management

Retraction Note

Retraction Note to: Effect of miR-451 on the Biological Behavior of the Esophageal Carcinoma Cell Line EC9706

Original Article

Multifocal Versus Conventional Unifocal Diverticulitis: A Comparison of Clinical and Transcriptomic Characteristics

Correspondence

Glypican-1 as a Therapy Target in Esophageal Squamous Cell Carcinoma

Original Article

Association of Serum Levels of Silent Information Regulator 1 with Persistent Organ Failure in Acute Pancreatitis

Editorial

Some Like It Cold: Postpolypectomy Delayed Hemorrhage in Anticoagulated Patients
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits