Bioactive Whey Protein Concentrate and Lactose Stimulate Gut Function in Formula‐fed Preterm Pigs

Li, Yanqi; Nguyen, Duc Ninh; Obelitz-Ryom, Karina; Andersen, Anette; Thymann, Thomas; Chatterton, Dereck E.W.; Purup, Stig; Heckmann, Anne B.; Bering, Stine Brandt; Sangild, Per Torp

doi:10.1097/mpg.0000000000001699

Cited by 26 publications

(33 citation statements)

References 44 publications

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“…Fluorescence in situ hybridization was applied to paraformaldehyde‐fixed small‐intestinal slices to determine the density of mucosa‐adhering bacteria . The density of mucin‐containing goblet cells was determined using Alcian Blue–Periodic Acid Schiff–stained slides . Proinflammatory cytokines interleukin (IL)‐1β, IL‐6, and IL‐8 were measured by enzyme‐linked immunosorbent assay (ELISA).…”

Section: Methodsmentioning

confidence: 99%

“…A piece of liver from the lower lobes and bone marrow from the left femur were sampled aseptically. Macroscopic lesion on stomach, proximal, middle, and distal small intestine, and colon were scored (1)(2)(3)(4)(5)(6). Pigs with a score >3 in any of the 4 intestinal regions were diagnosed as severe NEC.…”

Section: Clinical Evaluation and Tissue Collectionmentioning

confidence: 99%

“…19 The density of mucin-containing goblet cells was determined using Alcian Blue-Periodic Acid Schiff-stained slides. 6 Proinflammatory cytokines interleukin (IL)-1β, IL-6, and IL-8 were measured by enzyme-linked immunosorbent assay (ELISA). Intestinal gene expression was measured by quantitative polymerase chain reaction as described previously, 19 and primers were synthesized by TAG (Copenhagen, Denmark; see primer sequences in Supplementary Table S1).…”

Section: Gut Function Morphology and Inflammationmentioning

confidence: 99%

“…Currently, most fortifier products are formula‐based fortifiers (FFs), manufactured from cow's milk products, vegetable oils and maltodextrin, and added minerals. Like infant formulas, FFs are subject to several processing and sterilization steps (ie, filtration, heat treatment, protein hydrolysis), potentially reducing the milk bioactivity …”

Section: Introductionmentioning

confidence: 99%

“…Like infant formulas, FFs are subject to several processing and sterilization steps (ie, filtration, heat treatment, protein hydrolysis), potentially reducing the milk bioactivity. 6 Despite that fortification is widely adopted for very preterm infants fed human milk, 1 there have been concerns that human milk fortification with formula-based fortifier (FF) increases the risk for necrotizing enterocolitis (NEC) and systemic infections, especially when the dose is high and fortification starts early. 7,8 Compared with infant formula and FFs, exclusively human milk diet (ie, DHM and human milk-based fortifier) is associated with less mortality and improved clinical outcomes including NEC in preterm infants.…”

Section: Introductionmentioning

confidence: 99%

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Human Milk Fortification with Bovine Colostrum Is Superior to Formula‐Based Fortifiers to Prevent Gut Dysfunction, Necrotizing Enterocolitis, and Systemic Infection in Preterm Pigs

Sun

Pan

et al. 2018

J Parenter Enteral Nutr

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Section: Methodsmentioning

confidence: 99%

Section: Clinical Evaluation and Tissue Collectionmentioning

confidence: 99%

Section: Gut Function Morphology and Inflammationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Human Milk Fortification with Bovine Colostrum Is Superior to Formula‐Based Fortifiers to Prevent Gut Dysfunction, Necrotizing Enterocolitis, and Systemic Infection in Preterm Pigs

Sun

Pan

et al. 2018

J Parenter Enteral Nutr

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Gastric Residual to Predict Necrotizing Enterocolitis in Preterm Piglets As Models for Infants

Kappel

Sangild

Hilsted

et al. 2020

J Parenter Enteral Nutr

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Background Necrotizing enterocolitis (NEC) is a serious intestinal inflammatory disease in preterm infants. High volume of gastric residual (GR) after oral feedings is often used as a predictor of NEC, but evidence is limited. Using NEC‐sensitive preterm piglets as models, we hypothesized that GR mass and related plasma biomarkers predict early onset of NEC. Methods In total, 258 newborn preterm piglets were fed bovine milk–based formulas for 5 days. At euthanasia, the stomach, small intestine, and colon were evaluated for NEC lesions. Mass, acidity, gastrin, and bile acid levels were determined for GR content, together with gastrin, glucagon‐like peptide 2 (GLP‐2), and gastric inhibitory polypeptide (GIP) levels in plasma. Results In total, 48% of piglets had NEC lesions in the small intestine and/or colon. These piglets had higher GR mass (+32%, P < 0.001) and lower gastric bile acid concentrations (−22%, P < 0.05) than piglets without NEC lesions. The positive and negative predictive values for these markers were 34%–61%. Gastric acidity, gastrin, GLP‐2, and GIP levels were similar for piglets with and without NEC lesions. Conclusion Elevated GR mass correlates positively with NEC lesions but may be a poor predictor of NEC, even when combined with other biomarkers. More knowledge about gastric emptying and gut transit in preterm neonates is required to understand how GR volume and composition relate to morbidities, such as NEC, in preterm neonates.

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Ultra‐High Temperature Treatment and Storage of Infant Formula Induces Dietary Protein Modifications, Gut Dysfunction, and Inflammation in Preterm Pigs

Sun

Akıllıoğlu

Aasmul‐Olsen

et al. 2022

Molecular Nutrition Food Res

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Scope: Ready-to-feed liquid infant formula is increasingly used for preterm infants when human milk is unavailable. These formulas are sterilized by ultra-high temperature treatment, but heating and storage may reduce bioactivity and increase formation of Maillard reaction products with potential negative consequences for immature newborns. Methods and results: Using preterm pigs as a model for sensitive newborn infants, the study tests the intestinal responses of feeding experimental liquid formula within 5 days. A pasteurized formula (PAST) with the same nutrient composition but less protein modifications serves as control to ultra-high temperature-treated formula without (UHT) and with prolonged storage (SUHT). Relative to PAST, UHT contains lower levels of lactoferrin and IgG. Additional storage (40 °C, 60 days, SUHT) reduces antimicrobial capacity and increases non-reducible protein aggregates and Maillard reaction products (up to 13-fold). Pigs fed SUHT have more diarrhea and show signs of intestinal inflammation (necrotizing enterocolitis) compared with pigs fed PAST and UHT. These clinical effects are accompanied by accumulation of Maillard reaction products, protein cross-links, and inflammatory responses in the gut. Conclusion: The results demonstrate that feeding UHT infant formulas, particularly after prolonged storage, adversely affects gut maturation and function in preterm pigs used as a model of preterm infants.

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Bioactive Whey Protein Concentrate and Lactose Stimulate Gut Function in Formula‐fed Preterm Pigs

Abstract: Infant formulas containing lactose as the main carbohydrate, and WPC with reduced thermal processing, may support gut maturation and health in sensitive, preterm neonates.

Cited by 26 publications

References 44 publications

Human Milk Fortification with Bovine Colostrum Is Superior to Formula‐Based Fortifiers to Prevent Gut Dysfunction, Necrotizing Enterocolitis, and Systemic Infection in Preterm Pigs

Human Milk Fortification with Bovine Colostrum Is Superior to Formula‐Based Fortifiers to Prevent Gut Dysfunction, Necrotizing Enterocolitis, and Systemic Infection in Preterm Pigs

Gastric Residual to Predict Necrotizing Enterocolitis in Preterm Piglets As Models for Infants

Ultra‐High Temperature Treatment and Storage of Infant Formula Induces Dietary Protein Modifications, Gut Dysfunction, and Inflammation in Preterm Pigs

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