Human milk improves the oral bioavailability of the poorly water-soluble drug clofazimine.

Clofazimine is an emerging drug for the treatment of cryptosporidiosis in infants. As a poorly water-soluble drug, the formulation of clofazimine in age-appropriate vehicles is challenging and often results in the use of off-label formulations. Milk-based vehicles such as human milk and bovine milk have been investigated as age-appropriate formulations and shown to increase the solubilisation of poorly water-soluble drugs via enhanced solubility in lipid digestion products in vitro.

Fecal virus-like particles are sufficient to reduce necrotizing enterocolitis.

Fecal filtrate transfer (FFT) is emerging as a safer alternative to traditional fecal microbiota transplantation (FMT) - particularly in the context of necrotizing enterocolitis (NEC), a severe gastrointestinal condition affecting preterm infants. Using a preterm piglet model, FFT has demonstrated superiority over FMT in safety and NEC prevention. Since FFT is virtually devoid of bacteria, prokaryotic viruses (bacteriophages) are assumed to mediate the beneficial effects.

Enteral plasma feeding improves gut function and immunity in piglets after birth asphyxia.

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.

Bovine colostrum prevents formula-induced gut microbiota dysbiosis in preterm pigs.

Background: Preterm birth and formula feeding increase the risk of necrotizing enterocolitis (NEC), a gut inflammatory disease known to be associated with gut microbiota (GM) changes in infants. Supplemental bovine colostrum may protect against formula-induced NEC via GM changes. We hypothesised that feeding colostrum before, after, or during formula feeding affects NEC sensitivity via changes to GM.

Cord Obstruction and Delayed Cord Clamping Do Not Affect Gut Function in Neonatal Piglets.

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.

Insulin-like growth factor-1 effects on kidney development in preterm piglets.

Background: Preterm birth disrupts fetal kidney development, potentially leading to postnatal acute kidney injury. Preterm infants are deficient in insulin-like growth factor 1 (IGF-1), a growth factor that stimulates organ development. By utilizing a preterm pig model, this study investigated whether IGF-1 supplementation enhances preterm kidney maturation.

Enteral plasma supports brain repair in newborn pigs after birth asphyxia.

Newborns exposed to birth asphyxia transiently experience deficient blood flow and a lack of oxygen, potentially inducing hypoxic-ischaemic encephalopathy and subsequent neurological damage. Immunomodulatory components in plasma may dampen these responses. Using caesarean-delivered pigs as a model, we hypothesized that dietary plasma supplementation improves brain outcomes in pigs exposed to birth asphyxia.

Skeletal consequences of preterm birth in pigs as a model for preterm infants.

Preterm birth affects about 10% of all live births with many resultant health challenges, including metabolic bone disease of prematurity (MBDP), which is characterized by elevated alkaline phosphatase, suppressed phosphate, and deficient skeletal development. Because of the lack of an animal model, very little is known about bone structure, strength, and quality after preterm birth. This study investigated the utility of a pig model to replicate clinical features of preterm birth, including MBDP, and sought to determine if early postnatal administration of IGF-1 was an effective treatment.

A Gently Processed Skim Milk-Derived Whey Protein Concentrate for Infant Formula: Effects on Gut Development and Immunity in Preterm Pigs.

Scope: Processing of whey protein concentrate (WPC) for infant formulas may induce protein modifications with severe consequences for preterm newborn development. The study investigates how conventional WPC and a gently processed skim milk-derived WPC (SPC) affect gut and immune development after birth.

Methods And Results: Newborn, preterm pigs used as a model of preterm infants were fed formula containing WPC, SPC, extra heat-treated SPC (HT-SPC), or stored HT-SPC (HTS-SPC) for 5 days.

Adverse Metabolic Phenotypes in Parenterally Fed Neonatal Pigs Do Not Persist into Adolescence.

Background: Nutrition during fetal and neonatal life is an important determinant for the risk of adult-onset diseases, especially type 2 diabetes and obesity.

Objectives: We aimed to determine whether total parenteral nutrition (TPN) compared with enteral formula feeding [enteral nutrition (EN)] in term piglets during the first 2 wk after birth would increase the long-term (5-mo) development of metabolic syndrome phenotypes with adverse glucose homeostasis, fatty liver disease, and obesity.

Methods: Neonatal female pigs were administered TPN (n = 12) or fed enterally with a liquid enteral milk-replacer formula (EN, n = 12) for 14 d.

Effects of early postnatal gastric and colonic microbiota transplantation on piglet gut health.

Background: Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry. Diarrhea and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the gut. To secure better postnatal gut colonization, we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning period.

Gut development following insulin-like growth factor-1 supplementation to preterm pigs.

Background: Reduced insulin-like growth factor-1 (IGF-1) levels may contribute to impaired organ development in preterm infants. Using preterm pigs as a model, we hypothesized that IGF-1 supplementation improves health and gut development during the first three weeks of life.

Methods: First, clinical and organ endpoints were compared between artificially-reared, cesarean-delivered preterm pigs and vaginally-delivered, sow-reared term pigs at 5, 9 and 19 days.

Insulin-like growth factor 1 supplementation supports motor coordination and affects myelination in preterm pigs.

Introduction: Preterm infants have increased risk of impaired neurodevelopment to which reduced systemic levels of insulin-like growth factor 1 (IGF-1) in the weeks after birth may play a role. Hence, we hypothesized that postnatal IGF-1 supplementation would improve brain development in preterm pigs, used as a model for preterm infants.

Methods: Preterm pigs delivered by cesarean section received recombinant human IGF-1/IGF binding protein-3 complex (rhIGF-1/rhIGFBP-3, 2.

Towards a model of biliary atresia - Pilot feasibility study in newborn piglets.

Biliary atresia (BA) is a rare congenital liver disease with unknown etiology, and it is the most common indication for liver transplantation in children. As BA infants suffer from intestinal malabsorption and neurodevelopmental deficits, it is necessary to identify optimal medical and nutritional strategies using appropriate neonatal animal models. We aim to determine the feasibility of using newborn piglets with surgically induced cholestasis (bile duct ligation (BDL)) to mimic clinical features of BA.

Ontogeny of CYP3A and UGT activity in preterm piglets: a translational model for drug metabolism in preterm newborns.

Despite considerable progress in understanding drug metabolism in the human pediatric population, data remains scarce in preterm neonates. Improving our knowledge of the ADME properties in this vulnerable age group is of utmost importance to avoid suboptimal dosing, which may lead to adverse drug reactions. The juvenile (mini)pig is a representative model for hepatic drug metabolism in human neonates and infants, especially phase I reactions.

Transplantation of fecal filtrate to neonatal pigs reduces post-weaning diarrhea: A pilot study.

Post-weaning diarrhea (PWD) remains a major source of mortality and morbidity in swine production. Transplantation of bacteria-free filtrate of feces (fecal filtrate transplant, FFT) has shown gut protective effects in neonatal pigs, and early postnatal establishment of the gut microbiome is suggested to determine later stability and robustness of the gut. We, therefore, hypothesized that early postnatal transplantation of bacteria-free feces would have a protective effect against PWD.

Insulin-Like Growth Factor-1 Supplementation Promotes Brain Maturation in Preterm Pigs.

Very preterm infants show low levels of insulin-like growth factor-1 (IGF-1), which is associated with postnatal growth restriction and poor neurologic outcomes. It remains unknown whether supplemental IGF-1 may stimulate neurodevelopment in preterm neonates. Using cesarean-delivered preterm pigs as a model of preterm infants, we investigated the effects of supplemental IGF-1 on motor function and on regional and cellular brain development.

Uncovering the gastrointestinal passage, intestinal epithelial cellular uptake, and AGO2 loading of milk miRNAs in neonates using xenomiRs as tracers.

Background: Human breast milk has a high microRNA (miRNA) content. It remains unknown whether and how milk miRNAs might affect intestinal gene regulation and homeostasis of the developing microbiome after initiating enteral nutrition. However, this requires that relevant milk miRNA amounts survive the gastrointestinal (GI) passage, are taken up by cells, and become available to the RNA interference machinery.

Neonatal prophylactic antibiotics after preterm birth affect plasma proteome and immune development in pigs.

Background: Most preterm infants receive antibiotics to prevent serious infections shortly after birth. However, prolonged antibiotic treatment predisposes to gut dysbiosis and late-onset sepsis. Using preterm pigs as model, we hypothesized that neonatal prophylactic antibiotics impair systemic immune development beyond the days of antibiotic treatment.

Clinical outcome and gut development after insulin-like growth factor-1 supplementation to preterm pigs.

Background: Elevation of circulating insulin-like growth factor-1 (IGF-1) within normal physiological levels may alleviate several morbidities in preterm infants but safety and efficacy remain unclear. We hypothesized that IGF-1 supplementation during the first 1-2 weeks after preterm birth improves clinical outcomes and gut development, using preterm pigs as a model for infants.

Methods: Preterm pigs were given vehicle or recombinant human IGF-1/binding protein-3 (rhIGF-1, 2.

Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets.

Infants with neonatal cholestasis are prone to neurodevelopmental deficits, however, the underlying pathogenesis is unclear. Lipid malabsorption and accumulation of potentially neurotoxic molecules in the blood such as bile acids are important yet relatively unexplored pathways. Here, we developed a translational piglet model to understand how the molecular bile acid and lipid composition of the brain is affected by this disease and relates to motor function.

Donor-dependent fecal microbiota transplantation efficacy against necrotizing enterocolitis in preterm pigs.

The development of necrotizing enterocolitis (NEC), a life-threatening inflammatory bowel disease affecting preterm infants, is connected with gut microbiota dysbiosis. Using preterm piglets as a model for preterm infants we recently showed that fecal microbiota transplantation (FMT) from healthy suckling piglet donors to newborn preterm piglets decreased the NEC risk. However, in a follow-up study using donor stool from piglets recruited from another farm, this finding could not be replicated.

Brain lipidomics and neurodevelopmental outcomes in intrauterine growth restricted piglets fed dairy or vegetable fat diets.

Breast milk has neurodevelopmental advantages compared to infant formula, especially in low-birth-weight infants, which may in part relate to the fat source. This study compared neurodevelopmental outcomes in three-day-old normal birth weight (NBW) and intrauterine growth restricted (IUGR) piglets fed a formula diet with either vegetable oil (VEG) or bovine milk fat sources (MILK) for three weeks in a 2 × 2 factorial design. Behavioural tests, lipidomics, MRI and RNA sequencing analyses of plasma and brain tissue were conducted.

Differential Brain and Cerebrospinal Fluid Proteomic Responses to Acute Prenatal Endotoxin Exposure.

Chorioamnionitis (CA) is a risk factor for preterm birth and is associated with neurodevelopmental delay and cognitive disorders. Prenatal inflammation-induced brain injury may resolve during the immediate postnatal period when rapid brain remodeling occurs. Cerebrospinal fluid (CSF) collected at birth may be a critical source of predictive biomarkers.