Introducing Enteral Feeding Induces Intestinal Subclinical Inflammation and Respective Chromatin Changes in Preterm Pigs

Willems, Rhea; Krych, Łukasz; Rybicki, Verena; Jiang, Pingping; Sangild, Per T.; Shen, René Liang; Hensel, Kai O.; Wirth, Stéfan; Postberg, Jan; Jenke, Andreas

doi:10.2217/epi.15.13

Cited by 32 publications

(32 citation statements)

References 52 publications

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“…CXCL10 encodes a chemokine ligand CXCL10 for the CXCR3 receptor leading to immune stimulation, consistent with increased expression in the colon after dextran sulfate-induced ulceration in mice (61). We observed increased IF-related TLR2 expression (gram-positive G320 DIET AND EARLY FEEDING FOR PRETERM NEONATES bacterial receptor), consistent with some rat NEC studies (36) but limited effects on expression of the gram negative bacterial receptor, TLR4, consistent with our earlier studies in preterm pigs (4,48,63,69). A subset of samples from the middle intestine was used to investigate intestinal inflammation and immunity genes in more detail, including their chromatin structures (69).…”

Section: Discussionsupporting

confidence: 91%

“…After feeding preterm pigs for 5 days, NEC lesions and a series of gut structural, functional, immunological, and microbiological parameters were measured. Some of the preterm pigs in this study were previously used to show how the first enteral feeding increases physical activity (11) and a series of intestinal inflammatory and pattern recognition receptor genes with corresponding changes in chromatin structures (69).…”

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confidence: 99%

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Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs

Shen

Thymann

Østergaard

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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Shen RL, Thymann T, Østergaard MV, Støy AC, Krych Ł, Nielsen DS, Lauridsen C, Hartmann B, Holst JJ, Burrin DG, Sangild PT. 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 309: G310 -G323, 2015. First published July 2, 2015; doi:10.1152/ajpgi.00163.2015.-It is unclear when and how to start enteral feeding for preterm infants when mother's milk is not available. We hypothesized that early and slow advancement with either formula or bovine colostrum stimulates gut maturation and prevents necrotizing enterocolitis (NEC) in preterm pigs, used as models for preterm infants. Pigs were given either total parenteral nutrition (TPN, n ϭ 14) or slowly advancing volumes (16 -64 ml·kg Ϫ1 ·day Ϫ1 ) of preterm infant formula (IF, n ϭ 15) or bovine colostrum (BC, n ϭ 13), both given as adjunct to parenteral nutrition. On day 5, both enteral diets increased intestinal mass (27 Ϯ 1 vs. 22 Ϯ 1 g/kg) and glucagon-like peptide 2 release, relative to TPN (P Ͻ 0.05). The incidence of mild NEC lesions was higher in IF than BC and TPN pigs (60 vs. 0 and 15%, respectively, P Ͻ 0.05). Only the IF pigs showed reduced gastric emptying and gastric inhibitory polypeptide release, and increased tissue proinflammatory cytokine levels (IL-1␤ and IL-8, P Ͻ 0.05) and expression of immunerelated genes (AOAH, LBP, CXCL10, TLR2), relative to TPN. The IF pigs also showed reduced intestinal villus-to-crypt ratio, lactose digestion, and some plasma amino acids (Arg, Cit, Gln, Tyr, Val), and higher intestinal permeability, compared with BC pigs (all P Ͻ 0.05). Colonic microbiota analyses showed limited differences among groups. Early feeding with formula induces intestinal dysfunction whereas bovine colostrum supports gut maturation when mother's milk is absent during the first week after preterm birth. A dietdependent feeding guideline may be required for newborn preterm infants.

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Section: Discussionsupporting

confidence: 91%

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confidence: 99%

Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs

Shen

Thymann

Østergaard

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Our results show that the developmental expression of these enzymes is relatively independent of environmental factors, such as diet (which was the same for preterm and term pigs), and that intrinsic mechanisms related to ontogenetic age and genetic control could be more important. We recently documented that both preterm birth and enteral food introduction induce epigenetic effects on some immune-related genes in the immature pig intestine (19,53). It will be important to know whether preterm birth also induces epigenetic modifications to the sucrase-isomaltase and maltaseglucoamylase genes because this may help to explain why their corresponding enzyme activities were affected more long term whereas other gene functions tended to adapt more rapidly after preterm birth.…”

Section: Discussionmentioning

confidence: 99%

“…On day 5, the PN was discontinued and all piglets were given increasing amounts of raw bovine milk (64 -150 ml·kg Ϫ1 ·day Ϫ1 ) to day 9 and subsequently transferred to reconstituted whole milk powder at 150 -200 ml·kg Ϫ1 ·day Ϫ1 (Arla Foods Ingredients, Viby, Denmark) until day 26. The dosing strategies for both TPN and enteral feeding are comparable with the feeding advancement rates used for moderately preterm infants (4,13,17,25,53). See Fig.…”

Section: Animals and Nutritionmentioning

confidence: 92%

Rapid gut growth but persistent delay in digestive function in the postnatal period of preterm pigs

Hansen

Thymann

Andersen

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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Preterm infants often tolerate full enteral nutrition a few weeks after birth but it is not known how this is related to gut maturation. Using pigs as models, we hypothesized that intestinal structure and digestive function are similar in preterm and term individuals at 3-4 wk after birth and that early enteral nutrition promotes maturation. Preterm or term cesareandelivered pigs were fed total parenteral nutrition, or partial enteral nutrition [Enteral (Ent), 16 -64 ml·kg Ϫ1 ·day Ϫ1 of bovine colostrum] for 5 days, followed by full enteral milk feeding until day 26. The intestine was collected for histological and biochemical analyses at days 0, 5, and 26 (n ϭ 8 -12 in each of 10 treatment groups). Intestinal weight (relative to body weight) was reduced in preterm pigs at 0 -5 days but ENT feeding stimulated the mucosal volume and peptidase activities. Relative to term pigs, mucosal volume remained reduced in preterm pigs until 26 days although plasma glucagon-like peptide 2 (GLP-2) and glucose-dependent insulin-trophic peptide (GIP) levels were increased. Preterm pigs also showed reduced hexose absorptive capacity and brush-border enzyme (sucrase, maltase) activities at 26 days, relative to term pigs. Intestinal structure shows a remarkable growth adaptation in the first week after preterm birth, especially with enteral nutrition, whereas some digestive functions remain immature until at least 3-4 wk. It is important to identify feeding regimens that stimulate intestinal maturation in the postnatal period of preterm infants because some intestinal functions may show long-term developmental delay. prematurity; gut development; enzymes; digestion; glucagon-like peptide 2 ABOUT 10% OF ALL INFANTS are born preterm (Ͻ37 weeks of gestation) and the proportion is increasing in most countries (6). Preterm infants show an increased susceptibility to infections, respiratory distress syndrome, intracranial hemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity, extrauterine growth restriction, neurodevelopmental disturbances, and necrotizing enterocolitis (NEC) (21, 31). The challenges are inversely related to gestational age at birth and the most severe adaptation problems occur during the first few weeks after birth. If preterm infants survive the difficult neonatal period, their body functions often adapt well, although some organ systems may show long-term developmental delay or deficits (18). It remains unknown how different organ systems adapt in preterm infants and when parameters of structure and function become similar to those in term infants. For gastrointestinal (GI) functions, eating disorders and dysregulated appetite have been reported in preterm infants (44) but very little is known about the long-term adaptation of the GI tract in preterm neonates.Investigations of postnatal GI adaptation in preterm neonates are difficult without an animal model that combines preterm birth, high NEC risk, and clinically relevant feeding interventions, such as parenteral and enteral nutrition. Piglets delivere...

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“…Human milk and other enterally given products change gene expression especially with methylation [38]. In studies performed in preterm infants and pig models, it was shown that proinflamatory genes became upregulated by enteral feeding [39] [40]. Also important risk factors in NEC pathogenesis such as intestinal microflora and intestinal splanhcnic perfusion has mutual interaction with enteral feeding type [41] [42].…”

Section: Enteral Feedingmentioning

confidence: 99%

New Frontiers of Necrotizing Enterocolitis: From Pathophysiology to Treatment

Zubarioglu¹,

Uslu²,

Bülbül³

2017

Health

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Necrotizing enterocolitis [NEC] is an inflammatory disease of intestine largely occuring in preterm infants with a wide range of damage from minimal injury limited to mucosa to extensive necrosis of bowel wall and perforation. Despite advancements in neonatal care, mortality remains high [30% -50%] and controversy still persists with regards to the most appropriate management of neonates with necrotizing enterocolitis. The main factors thought to be involved in the pathogenesis of NEC are: relatively hyper-reactive state of premature intestine, enteral feeding and bacterial colonization. In this review, we discuss current knowledge about the epidemiology, pathophysiology, imaging, medical and surgical management of necrotizing enterocolitis and describe novel strategies for prevention and treatment.

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Introducing Enteral Feeding Induces Intestinal Subclinical Inflammation and Respective Chromatin Changes in Preterm Pigs

Abstract: Enteral feeding, particular with formula, induces subclinical inflammation in the premature intestine and more open chromatin structure in key inflammatory genes. This may increase the susceptibility for necrotizing enterocolitis.

Cited by 32 publications

References 52 publications

Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs

Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs

Rapid gut growth but persistent delay in digestive function in the postnatal period of preterm pigs

New Frontiers of Necrotizing Enterocolitis: From Pathophysiology to Treatment

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