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Background: The human digestive tract is structurally mature at birth, yet maturation of gut functions such as digestion and mucosal barrier continues for the next 1-2 years. Human milk and infant milk formulas (IMF) seem to impact maturation of these gut functions differently, which is at least partially related to high temperature processing of IMF causing loss of bioactive proteins and formation of advanced glycation end products (AGEs). Both loss of protein bioactivity and formation of AGEs depend on heating temperature and time. The aim of this study was to investigate the impact of mildly pasteurized whey protein concentrate (MP-WPC) compared to extensively heated WPC (EH-WPC) on gut maturation in a piglet model hypersensitive to enteral nutrition.
Methods: WPC was obtained by cold filtration and mildly pasteurized (73 °C, 30 s) or extensively heat treated (73 °C, 30 s + 80 °C, 6 min). Preterm (~90% gestation) and near-term piglets (~96% gestation) received enteral nutrition based on MP-WPC or EH-WPC for five days. Macroscopic and histologic lesions in the gastro-intestinal tract were evaluated and intestinal responses were further assessed by RT-qPCR, immunohistochemistry and enzyme activity analysis.
Results: A diet based on MP-WPC limited epithelial intestinal damage and improved colonic integrity compared to EH-WPC. MP-WPC dampened colonic IL1-β, IL-8 and TNF-α expression and lowered T-cell influx in both preterm and near-term piglets. Anti-microbial defense as measured by neutrophil influx in the colon was only observed in near-term piglets, correlated with histological damage and was reduced by MP-WPC. Moreover, MP-WPC stimulated iALP activity in the colonic epithelium and increased differentiation into enteroendocrine cells compared to EH-WPC.
Conclusions: Compared to extensively heated WPC, a formula based on mildly pasteurized WPC limits gut inflammation and stimulates gut maturation in preterm and near-term piglets and might therefore also be beneficial for preterm and (near) term infants.
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http://dx.doi.org/10.3390/nu12041125 | DOI Listing |
Semin Perinatol
August 2025
Department of Physiology, University of Auckland, New Zealand. Electronic address:
Neonatal hypoxic-ischemic encephalopathy (HIE) remains a major cause of death and disability around the world. Therapeutic hypothermia is now established to improve outcomes in term and near-term infants in high-income countries, but even in this setting, many infants still survive with disability. To further improve outcomes, experimental models are needed to test new interventions before clinical translation.
View Article and Find Full Text PDFPediatr Res
February 2025
Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Introduction: Birth asphyxia may negatively affect gut function and immunity in newborns. Conversely, immunomodulatory milk diets may protect the gut and immune system against damage caused by asphyxia. Using caesarean-derived pigs as models, we hypothesised that enteral feeding with plasma improves gut and immune functions in asphyxiated newborns.
View Article and Find Full Text PDFNeonatology
April 2025
Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Introduction: Birth-related obstruction of umbilical blood flow may induce hypoxic insults that affect postnatal organ adaptation. Using newborn cesarean-delivered pigs, we hypothesized that cord obstruction during delivery negatively affects physiological transition and gut maturation. Further, we investigated if delayed cord clamping (DCC) improves gut outcomes, including sensitivity to formula-induced necrotizing enterocolitis (NEC)-like lesions.
View Article and Find Full Text PDFJ Nutr
July 2024
Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark. Electronic address:
Background: β-casein is the main casein constituent in human milk (HM) and a source of bioactive peptides for the developing gastrointestinal tract and immune system. Infant formulas contain less β-casein than HM, but whether different concentrations of β-casein affect tolerability and gut and immune maturation in newborns is unknown.
Objectives: Using near-term piglets as a model for newborn infants, we investigated whether increasing the β-casein fraction in bovine-based formula is clinically safe and may improve gut and immune maturation.
Front Pediatr
January 2021
Comparative Pediatrics and Nutrition, University of Copenhagen, Copenhagen, Denmark.
Gut motility in infants mature with increasing post-menstrual age and is affected by numerous hormonal, immunological and nutritional factors. However, it remains unclear how age and diet influence gut motility and its relation to feeding intolerance and gastric residuals in preterm neonates. Using preterm piglets as a model for infants, we investigated if contrast passage rate, as determined by X-ray contrast imaging, is affected by gestational age at birth, advancing postnatal age and different milk diets.
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