Aldohexose Malabsorption in Preterm Pigs Is Directly Related to the Severity of Necrotizing Enterocolitis

Buddington, Randal K.; Bering, Stine Brandt; Thymann, Thomas; Sangild, Per Torp

doi:10.1203/pdr.0b013e318165bfed

Cited by 26 publications

(21 citation statements)

References 40 publications

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“…Although intact tissue uptakes were lower in the middle and distal regions of the small intestine of the pigs fed the maltodextrin-based formula, the majority of sugar absorption occurs in the proximal region. Importantly, despite a lack of overt signs of NEC, in vivo and ex vivo aldohexose absorption by the pigs infused with the lactose-based formula after 36 h was Ͻ20% of that measured for colostrum-fed pigs in our previous study (6).…”

Section: Discussioncontrasting

confidence: 59%

Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs

Thymann

Möller

Stoll

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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112

126

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Necrotizing enterocolitis (NEC) remains the most severe gastrointestinal disorder in preterm infants. It is associated with the initiation of enteral nutrition and may be related to immature carbohydrate digestive capacity. We tested the hypothesis that a formula containing maltodextrin vs. a formula containing lactose as the principal source of carbohydrate would predispose preterm pigs to a higher NEC incidence. Cesarean-derived preterm pigs were given total parenteral nutrition for 48 h followed by total enteral nutrition with a lactose-based (n = 11) or maltodextrin-based (n = 11) formula for 36 h. A higher incidence (91% vs. 27%) and severity (score of 3.3 vs. 1.8) of NEC were observed in the maltodextrin than in the lactose group. This higher incidence of NEC in the maltodextrin group was associated with significantly lower activities of lactase, maltase, and aminopeptidase; reduced villus height; transiently reduced in vivo aldohexose uptake; and reduced ex vivo aldohexose uptake capacity in the middle region of the small intestine. Bacterial diversity was low for both diets, but alterations in bacterial composition and luminal concentrations of short-chain fatty acids were observed in the maltodextrin group. In a second study, we quantified net portal absorption of aldohexoses (glucose and galactose) during acute jejunal infusion of a maltodextrin- or a lactose-based formula (n = 8) into preterm pigs. We found lower net portal aldohexose absorption (4% vs. 42%) and greater intestinal recovery of undigested carbohydrate (68% vs. 27%) in pigs acutely perfused with the maltodextrin-based formula than those perfused with the lactose-based formula. The higher digestibility of the lactose than the maltodextrin in the formulas can be attributed to a 5- to 20-fold higher hydrolytic activity of tissue-specific lactase than maltases. We conclude that carbohydrate maldigestion is sufficient to increase the incidence and severity of NEC in preterm pigs.

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Section: Discussioncontrasting

confidence: 59%

Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs

Thymann

Möller

Stoll

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

Self Cite

112

126

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“…The present study shows that the digestive capacity starts to be affected already at mild signs of NEC (score of 3-4), although more marked changes are only associated with severe NEC (score of 5-6). The expression of SLC5A1 (involved in hexose absorption) was not affected by increased NEC severity, indicating that the lower hexose absorption observed with increasing NEC severity in pigs [29] is not due to downregulation of the related gene. NEC development in both preterm pigs and infants is highly diet dependent and it is often difficult to ascertain when changes in intestinal function occur as a result of NEC progression, independently of the diet.…”

Section: Discussionmentioning

confidence: 99%

Increased Intestinal Inflammation and Digestive Dysfunction in Preterm Pigs with Severe Necrotizing Enterocolitis

Støy

Heegaard²,

Skovgaard³

et al. 2016

Neonatology

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Background: The risk factors for necrotizing enterocolitis (NEC) are well known, but the factors involved in the different NEC presentations remain unclear. Objectives: We hypothesized that digestive dysfunction and intestinal inflammation are mainly affected by severe NEC lesions. Methods: In 48 preterm pigs, the association between the macroscopic NEC score (range 1-6) and the expression of 48 genes related to inflammation, morphological, and digestive parameters in the distal small intestine was investigated. Results: Only severe NEC cases (score of 5-6) were associated with the upregulation of genes involved in inflammation (CCL2, CCL3, CD14, CD163, CXCL8, HP, IL1B, IL1RN, IL6,IL10, NFKBIA, PTGS2 and TNFAIP3) compared to pigs that appeared healthy (score of 1-2) or showed mild NEC (score of 3-4). Pigs with a score of 5-6 had higher intestinal tissue IL-1β levels and a lower mucosal mass, villus height, and aminopeptidase N activity compared to pigs with a score of 1-4, and lower crypts and activities of lactase, dipeptidylpeptidase IV, and aminopeptidase A than pigs with a score of 1-2. Conclusions: The expression of a range of inflammation-related genes was increased only in pigs with severe NEC, concomitant with morphological changes and decreased hydrolase activity. A severe inflammatory response and digestive dysfunction are associated mainly with severe NEC. Still, it remains difficult to separate the initial causes of NEC and the later intestinal consequences of NEC in both infants and experimental models.

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“…The carrier-mediated galactose transport occurs via the sodiumglucose linked transporter 1 (SGLT-1) that is located mainly in the upper part of the villi in the Prox and Mid (50). The differences observed in galactose transport among groups may relate to a combination of changes in mucosal mass and density of functional transporters (51). Interestingly, the concentrations of plasma citrulline, a marker of mucosal mass (52), were positively correlated with villus height and galactose absorption and were also lower in the CF and GF pigs than in the MF and BC pigs.…”

Section: Discussionmentioning

confidence: 99%

Whey Protein Processing Influences Formula-Induced Gut Maturation in Preterm Pigs

Østergaard

Jiang

et al. 2013

The Journal of Nutrition

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Immaturity of the gut predisposes preterm infants to nutritional challenges potentially leading to clinical complications such as necrotizing enterocolitis. Feeding milk formulas is associated with greater risk than fresh colostrum or milk, probably due to loss of bioactive proteins (e.g., immunoglobulins, lactoferrin, insulin-like growth factor, transforming growth factor-β) during industrial processing (e.g., pasteurization, filtration, spray-drying). We hypothesized that the processing method for whey protein concentrate (WPC) would affect gut maturation in formula-fed preterm pigs used as a model for preterm infants. Fifty-five caesarean-delivered preterm pigs were distributed into 4 groups given 1 of 4 isoenergetic diets: formula containing conventional WPC (filtration, multi-pasteurization, standard spray-drying) (CF); formula containing gently treated WPC (reduced filtration and pasteurization, gentle spray-drying) (GF); formula containing minimally treated WPC (rennet precipitation, reduced filtration, heat treatment <40°C, freeze-drying) (MF); and bovine colostrum (used as a positive reference group) (BC). Relative to CF, GF, and MF pigs, BC pigs had greater villus heights, lactose digestion, and absorption and lower gut permeability (P < 0.05). MF and BC pigs had greater plasma citrulline concentrations than CF and GF pigs and intestinal interleukin-8 was lower in BC pigs than in the other groups (P < 0.05). MF pigs had lower concentrations of intestinal claudin-4, cleaved caspase-3, and phosphorylated c-Jun than CF pigs (P < 0.05). The conventional and gently treated WPCs had similar efficacy in stimulating proliferation of porcine intestinal epithelial cells. We conclude that processing of WPC affects intestinal structure, function, and integrity when included in formulas for preterm pigs. Optimization of WPC processing technology may be important to preserve the bioactivity and nutritional value of formulas for sensitive newborns.

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Aldohexose Malabsorption in Preterm Pigs Is Directly Related to the Severity of Necrotizing Enterocolitis

Cited by 26 publications

References 40 publications

Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs

Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs

Increased Intestinal Inflammation and Digestive Dysfunction in Preterm Pigs with Severe Necrotizing Enterocolitis

Whey Protein Processing Influences Formula-Induced Gut Maturation in Preterm Pigs

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