Preterm birth makes the immature intestine sensitive to feeding-induced intestinal atrophy

Preterm birth and formula feeding predispose to small intestinal dysfunction, which may lead to necrotizing enterocolitis (NEC). In piglets, we tested whether the physiological and environmental transitions occurring at birth affect the response of the immature intestine to enteral feeding. Pig fetuses (106 days gestation, term = 115 days) were prepared with esophageal feeding tubes and fed either sow's colostrum ( n = 8) or infant formula ( n = 7) in utero. After 24 h of oral feeding, the pig fetuses were delivered by cesarean section and their gastrointestinal morphology and function were compared with those of preterm newborn (NB) littermates that were not fed ( n = 8) or fed colostrum ( n = 7) or formula ( n = 13) for 24 h after birth. Before birth, both colostrum and formula feeding resulted in marked increases in intestinal mass, brush-border enzyme activities, and plasma glucagon-like peptide 2 concentrations, to levels similar to those in NB colostrum-fed piglets. In contrast, NB formula-fed piglets showed reduced intestinal growth, decreased brush-border enzyme activities, and intestinal lesions, reflecting NEC. NB formula-fed pigs also showed impaired enterocyte endocytotic function and decreased antioxidative capacity, whereas brush-border enzyme mRNA levels were unaltered, relative to NB colostrum-fed pigs. Our results indicate that the feeding-induced growth and enzyme maturation of the immature intestine are not birth dependent. However, with a suboptimal diet (milk formula), factors related to preterm birth (e.g., microbial colonization and metabolic and endocrine changes) make the immature intestine sensitive to atrophy and development of NEC.

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Elective cesarean delivery affects gut maturation and delays microbial colonization but does not increase necrotizing enterocolitis in preterm pigs

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00705.2007 ◽

2008 ◽

Vol 294 (3) ◽

pp. R929-R938 ◽

Cited By ~ 39

Author(s):

R. H. Siggers ◽

T. Thymann ◽

B. B. Jensen ◽

L. Mølbak ◽

P. M. H. Heegaard ◽

...

Keyword(s):

Necrotizing Enterocolitis ◽

Brush Border ◽

Blood Chemistry ◽

Initial Study ◽

Microbial Colonization ◽

Milk Formula ◽

Metabolic Functions ◽

Elective Cesarean ◽

Initial Improvement ◽

Brush Border Enzyme

Although preterm birth and formula feeding increase the risk of necrotizing enterocolitis (NEC), the influences of cesarean section (CS) and vaginal delivery (VD) are unknown. Therefore, gut characteristics and NEC incidence and severity were evaluated in preterm pigs (92% gestation) delivered by CS or VD. An initial study showed that newborn CS pigs ( n = 6) had decreased gastric acid secretion, absorption of intact proteins, activity of brush-border enzymes and pancreatic hydrolases, plasma cortisol, rectal temperature, and changes in blood chemistry, indicating impaired respiratory function, compared with VD littermates ( n = 6). In a second experiment, preterm CS ( n = 16) and VD ( n = 16) pigs were given total parenteral nutrition (36 h) then fed porcine colostrum (VD-COL, n = 6; CS-COL, n = 6) or infant milk formula (VD-FORM, n = 10; CS-FORM, n = 10) for 2 days. Across delivery, FORM pigs showed significantly higher NEC incidence, tissue proinflammatory cytokines (IFN-γ and IL-6), Clostridium colonization, and impaired intestinal function, compared with COL pigs. NEC incidence was equal for CS (6/16) and VD (6/16) pigs, CS pigs had decreased bacterial diversity and density, higher villus heights, and increased brush-border enzyme activities (lactase, aminopeptidases) compared with VD pigs. In particular, VD-FORM pigs showed reduced mucosal proportions, reduced lactase and aminopeptidases, and increased proinflammatory cytokine IL-6 compared with CS-FORM ( P < 0.06). Despite the initial improvement of intestinal and metabolic functions following VD, gut function, and inflammation were similar, or more negatively affected in VD neonates than CS neonates. Both delivery modes exhibited positive and negative influences on the preterm gut, which may explain the similar NEC incidence.

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Brush border enzyme activities in the small intestine after long-term gliadin feeding in animal models of human cœliac disease

Folia Microbiologica ◽

10.1007/bf02820803 ◽

1998 ◽

Vol 43 (5) ◽

pp. 497-500 ◽

Cited By ~ 2

Author(s):

H. Kozáková ◽

R. Štěpánková ◽

J. Kolínská ◽

M. A. Farré ◽

D. P. Funda ◽

...

Keyword(s):

Small Intestine ◽

Animal Models ◽

Coeliac Disease ◽

Brush Border ◽

Enzyme Activities ◽

Brush Border Enzyme

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Pattern of rat intestinal brush-border enzyme gene expression changes with epithelial growth state

AJP Cell Physiology ◽

10.1152/ajpcell.1995.269.2.c385 ◽

1995 ◽

Vol 269 (2) ◽

pp. C385-C391 ◽

Cited By ~ 58

Author(s):

R. A. Hodin ◽

S. M. Chamberlain ◽

S. Meng

Keyword(s):

Gene Expression ◽

Alkaline Phosphatase ◽

Brush Border ◽

Longitudinal Axis ◽

Mrna Levels ◽

Intestinal Alkaline Phosphatase ◽

Enzyme Gene ◽

Growth State ◽

Brush Border Enzyme ◽

Epithelial Growth

Enterocyte growth and differentiation occur simultaneously within the epithelium, but little is known regarding any relationship between these two processes. Four rat models of small intestinal epithelial hypo- and hyperplasia (neonatal ontogeny, fasting/refeeding, hypo-/hyperthyroidism, and bombesin treatment) were used to study the regulation of enterocyte gene expression in relation to epithelial growth state. Mucosal scrapings, as well as crypt and villus cell populations, were subjected to Northern blot analyses using radiolabeled cDNA probes corresponding to lactase, intestinal alkaline phosphatase, villin, ornithine decarboxylase (ODC), and the actin control. In all four models, the hypoplastic (atrophic) condition is characterized by high levels of lactase and low levels of the 3.0-kb intestinal alkaline phosphatase mRNA, whereas under hyperplastic conditions this pattern is reversed. The changes in intestinal alkaline phosphatase and lactase are qualitatively similar along the longitudinal axis of the intestine and are proportional to the degree of hyperplasia, as verified by ODC mRNA levels. Furthermore, the crypt-villus axis of differentiation is maintained regardless of epithelial growth state. In conclusion, the pattern of brush-border enzyme gene expression changes as a function of epithelial growth state, indicating a previously unrecognized degree of plasticity to the state of enterocyte differentiation.

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