Factors Known to Influence the Development of Necrotizing Enterocolitis to Modify Expression and Activity of Intestinal Alkaline Phosphatase in a Newborn Neonatal Rat Model

Rebecca Maria Rentea; Matthea J. Rentea; Ben Biesterveld; Jennifer L. Liedel; David M. Gourlay

doi:10.1055/s-0038-1646959

European Journal of Pediatric Surgery, Table of Contents

Eur J Pediatr Surg 2019; 29(03): 290-297
DOI: 10.1055/s-0038-1646959

Original Article

Georg Thieme Verlag KG Stuttgart · New York

Factors Known to Influence the Development of Necrotizing Enterocolitis to Modify Expression and Activity of Intestinal Alkaline Phosphatase in a Newborn Neonatal Rat Model

Rebecca Maria Rentea

¹Department of Pediatric Surgery, Children's Mercy Hospital, Kansas City, Missouri, United States

,

Matthea J. Rentea

²Deparment of Medicine, Indiana University, Indianapolis, Indiana, United States

,

Ben Biesterveld

³Department of Surgery, University of Michigan, Ann Arbor, Michigan, United States

,

Jennifer L. Liedel

⁴Department of Pediatrics and Critical Care, Albert Einstein College of Medicine, Bronx, New York, United States

,

David M. Gourlay

⁵Division of Pediatric Surgery, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

› Author Affiliations

Abstract

Introduction Prematurity, formula feeding, and early weaning strongly influence enterocyte differentiation. Intestinal alkaline phosphatase (IAP), an endogenous protein expressed in the intestines, is one enzyme that is affected by these factors. IAP supplementation decreases the severity of necrotizing enterocolitis (NEC) injury. We, therefore, hypothesized that prematurity predisposes this population to NEC due to IAP deficiency and investigated IAP expression and function in a neonatal rat model.

Materials and Methods Pre- and full-term newborn Sprague-Dawley rat pups were sacrificed on consecutive days of life both after vaginal or cesarean birth and following either breast or formula feeding.

Results Compared with controls, cesarean delivery and formula feeding are associated with lower levels of IAP. The formula-fed pups continued to have low baseline IAP activity. Neither prematurity nor formula feeding led to differences of intestinal injury.

Conclusion Prematurity and formula feeding are associated with inhibition of IAP expression and activity. Both may increase the risk of NEC and early enteral supplementation of IAP to newborns at risk of NEC may be of therapeutic benefit.

Keywords

intestinal alkaline phosphatase - necrotizing enterocolitis - prematurity - breast milk - alkaline phosphatase

Full Text

References

References
1 Fitzgibbons SC, Ching Y, Yu D. , et al. Mortality of necrotizing enterocolitis expressed by birth weight categories. J Pediatr Surg 2009; 44 (06) 1072-1075
2 Rees CM, Eaton S, Pierro A. National prospective surveillance study of necrotizing enterocolitis in neonatal intensive care units. J Pediatr Surg 2010; 45 (07) 1391-1397
3 Hunter CJ, Upperman JS, Ford HR, Camerini V. Understanding the susceptibility of the premature infant to necrotizing enterocolitis (NEC). Pediatr Res 2008; 63 (02) 117-123
4 Rentea RM, Welak SR, Fredrich K. , et al. Early enteral stressors in newborns increase inflammatory cytokine expression in a neonatal necrotizing enterocolitis rat model. Eur J Pediatr Surg 2013; 23 (01) 39-47
5 Srivastava MD, Srivastava A, Brouhard B, Saneto R, Groh-Wargo S, Kubit J. Cytokines in human milk. Res Commun Mol Pathol Pharmacol 1996; 93 (03) 263-287
6 Feldman K, Woolcott C, O'Connell C, Jangaard K. Neonatal outcomes in spontaneous versus obstetrically indicated late preterm births in a nova scotia population. J Obstet Gynaecol Can 2012; 34 (12) 1158-1166
7 Claud EC, Lu L, Anton PM, Savidge T, Walker WA, Cherayil BJ. Developmentally regulated IkappaB expression in intestinal epithelium and susceptibility to flagellin-induced inflammation. Proc Natl Acad Sci U S A 2004; 101 (19) 7404-7408
8 Cilieborg MS, Boye M, Sangild PT. Bacterial colonization and gut development in preterm neonates. Early Hum Dev 2012; 88 (Suppl. 01) S41-S49
9 Alpers DH, Zhang Y, Ahnen DJ. Synthesis and parallel secretion of rat intestinal alkaline phosphatase and a surfactant-like particle protein. Am J Physiol 1995; 268 (6 Pt 1): E1205-E1214
10 Peters E, Mehta RL, Murray PT. , et al. Study protocol for a multicentre randomised controlled trial: Safety, Tolerability, efficacy and quality of life Of a human recombinant alkaline Phosphatase in patients with sepsis-associated Acute Kidney Injury (STOP-AKI). BMJ Open 2016; 6 (09) e012371
11 Pickkers P, Schouten J, Laterre PF. , et al. Alkaline phosphatase improves kidney function in ICU patients with sepsis-induced acute kidney injury. Intensive Care Med 2010; 36: S88
12 Malo MS, Moaven O, Muhammad N. , et al. Intestinal alkaline phosphatase promotes gut bacterial growth by reducing the concentration of luminal nucleotide triphosphates. Am J Physiol Gastrointest Liver Physiol 2014; 306 (10) G826-G838
13 Hyoju SK, Morrison S, Gul S. , et al. Intestinal alkaline phosphatase decreases intraperitoneal adhesion formation. J Surg Res 2017; 208: 84-92
14 Rentea RM, Liedel JL, Welak SR. , et al. Intestinal alkaline phosphatase administration in newborns is protective of gut barrier function in a neonatal necrotizing enterocolitis rat model. J Pediatr Surg 2012; 47 (06) 1135-1142
15 Kaliannan K, Hamarneh SR, Economopoulos KP. , et al. Intestinal alkaline phosphatase prevents metabolic syndrome in mice. Proc Natl Acad Sci U S A 2013; 110 (17) 7003-7008
16 Alam SN, Yammine H, Moaven O. , et al. Intestinal alkaline phosphatase prevents antibiotic-induced susceptibility to enteric pathogens. Ann Surg 2014; 259 (04) 715-722
17 Lallès JP. Intestinal alkaline phosphatase: novel functions and protective effects. Nutr Rev 2014; 72 (02) 82-94
18 Biesterveld BE, Koehler SM, Heinzerling NP. , et al. Intestinal alkaline phosphatase to treat necrotizing enterocolitis. J Surg Res 2015; 196 (02) 235-240
19 Rentea RM, Liedel JL, Fredrich K. , et al. Intestinal alkaline phosphatase administration in newborns decreases systemic inflammatory cytokine expression in a neonatal necrotizing enterocolitis rat model. J Surg Res 2012; 177 (02) 228-234
20 Riggle KM, Rentea RM, Welak SR, Pritchard Jr KA, Oldham KT, Gourlay DM. Intestinal alkaline phosphatase prevents the systemic inflammatory response associated with necrotizing enterocolitis. J Surg Res 2013; 180 (01) 21-26
21 Hodin RA, Meng S, Shei A. Differential cloning of novel intestine-specific genes whose expression is altered under conditions of villus atrophy. J Surg Res 1995; 59 (01) 115-120
22 Alkhoury F, Malo MS, Mozumder M, Mostafa G, Hodin RA. Differential regulation of intestinal alkaline phosphatase gene expression by Cdx1 and Cdx2. Am J Physiol Gastrointest Liver Physiol 2005; 289 (02) G285-G290
23 Lallès JP, Orozco-Solís R, Bolaños-Jiménez F, de Coppet P, Le Dréan G, Segain JP. Perinatal undernutrition alters intestinal alkaline phosphatase and its main transcription factors KLF4 and Cdx1 in adult offspring fed a high-fat diet. J Nutr Biochem 2012; 23 (11) 1490-1497
24 Goldberg RF, Austen Jr WG, Zhang X. , et al. Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition. Proc Natl Acad Sci U S A 2008; 105 (09) 3551-3556
25 Xu H, Shi Y, Wang J. , et al. A heat shock protein 90 binding domain in endothelial nitric-oxide synthase influences enzyme function. J Biol Chem 2007; 282 (52) 37567-37574
26 Akiba Y, Mizumori M, Guth PH, Engel E, Kaunitz JD. Duodenal brush border intestinal alkaline phosphatase activity affects bicarbonate secretion in rats. Am J Physiol Gastrointest Liver Physiol 2007; 293 (06) G1223-G1233
27 Rentea RM, Lam V, Biesterveld B. , et al. Radiation-induced changes in intestinal and tissue-nonspecific alkaline phosphatase: implications for recovery after radiation therapy. Am J Surg 2016; 212 (04) 602-608
28 Gomes JR, Ayub LC, Dos Reis CA. , et al. Goblet cells and intestinal alkaline phosphatase expression (IAP) during the development of the rat small intestine. Acta Histochem 2017; 119 (01) 71-77
29 Oste M, Van Haver E, Thymann T, Sangild P, Weyns A, Van Ginneken CJ. Formula induces intestinal apoptosis in preterm pigs within a few hours of feeding. JPEN J Parenter Enteral Nutr 2010; 34 (03) 271-279
30 Lackeyram D, Yang C, Archbold T, Swanson KC, Fan MZ. Early weaning reduces small intestinal alkaline phosphatase expression in pigs. J Nutr 2010; 140 (03) 461-468
31 Nanthakumar N, Meng D, Goldstein AM. , et al. The mechanism of excessive intestinal inflammation in necrotizing enterocolitis: an immature innate immune response. PLoS One 2011; 6 (03) e17776
32 Nanthakumar NN, Fusunyan RD, Sanderson I, Walker WA. Inflammation in the developing human intestine: a possible pathophysiologic contribution to necrotizing enterocolitis. Proc Natl Acad Sci U S A 2000; 97 (11) 6043-6048
33 Smith HW, Marshall CJ. Regulation of cell signalling by uPAR. Nat Rev Mol Cell Biol 2010; 11 (01) 23-36
34 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 (08) 1437-1444
35 Siggers J, Sangild PT, Jensen TK. , et al. Transition from parenteral to enteral nutrition induces immediate diet-dependent gut histological and immunological responses in preterm neonates. Am J Physiol Gastrointest Liver Physiol 2011; 301 (03) G435-G445
36 Siggers RH, Thymann T, Jensen BB. , et al. Elective cesarean delivery affects gut maturation and delays microbial colonization but does not increase necrotizing enterocolitis in preterm pigs. Am J Physiol Regul Integr Comp Physiol 2008; 294 (03) R929-R938
37 Fawley J, Gourlay DM. Intestinal alkaline phosphatase: a summary of its role in clinical disease. J Surg Res 2016; 202 (01) 225-234
38 Heinzerling NP, Liedel JL, Welak SR. , et al. Intestinal alkaline phosphatase is protective to the preterm rat pup intestine. J Pediatr Surg 2014; 49 (06) 954-960
39 Rentea RM, Liedel JL, Fredrich K. , et al. Enteral intestinal alkaline phosphatase administration in newborns decreases iNOS expression in a neonatal necrotizing enterocolitis rat model. J Pediatr Surg 2013; 48 (01) 124-128