Dual purpose use of preterm piglets as a model of pediatric GI disease

Oosterloo, Berthe C; Premkumar, Muralidhar H.; Stoll, Barbara J.; Olutoye, Oluyinka O.; Thymann, Thomas; Sangild, Per Torp; Burrin, Douglas G.

doi:10.1016/j.vetimm.2014.02.012

Cited by 21 publications

(16 citation statements)

References 123 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because of the difficulty of getting human intestinal samples during late fetal development, an alternative to currently used intestinal cell lines and organ cultures is to take the opportunity offered by animal models such as the pig that share similar physiologic and clinical features with humans. The pig is increasingly used as a hypersensitive model for pediatric gastroenterology [ 8 , 21 , 22 ]. The Large White (LW) breed, genetically-selected for lean growth and prolificacy, displays a high rate of mortality at birth due to a lower physiological maturity of newborn piglets, whereas the Chinese Meishan (MS) breed produces piglets with extremely low mortality rate although lighter birth weight [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Comparing the intestinal transcriptome of Meishan and Large White piglets during late fetal development reveals genes involved in glucose and lipid metabolism and immunity as valuable clues of intestinal maturity

et al. 2017

View full text Add to dashboard Cite

BackgroundMaturity of intestinal functions is critical for neonatal health and survival, but comprehensive description of mechanisms underlying intestinal maturation that occur during late gestation still remain poorly characterized. The aim of this study was to investigate biological processes specifically involved in intestinal maturation by comparing fetal jejunal transcriptomes of two representative porcine breeds (Large White, LW; Meishan, MS) with contrasting neonatal vitality and maturity, at two key time points during late gestation (gestational days 90 and 110). MS and LW sows inseminated with mixed semen (from breed LW and MS) gave birth to both purebred and crossbred fetuses. We hypothesized that part of the differences in neonatal maturity between the two breeds results from distinct developmental profiles of the fetal intestine during late gestation. Reciprocal crossed fetuses were used to analyze the effect of parental genome. Transcriptomic data and 23 phenotypic variables known to be associated with maturity trait were integrated using multivariate analysis with expectation of identifying relevant genes-phenotypic variable relationships involved in intestinal maturation.ResultsA moderate maternal genotype effect, but no paternal genotype effect, was observed on offspring intestinal maturation. Four hundred and four differentially expressed probes, corresponding to 274 differentially expressed genes (DEGs), more specifically involved in the maturation process were further studied. In day 110-MS fetuses, Ingenuity® functional enrichment analysis revealed that 46% of DEGs were involved in glucose and lipid metabolism, cell proliferation, vasculogenesis and hormone synthesis compared to day 90-MS fetuses. Expression of genes involved in immune pathways including phagocytosis, inflammation and defense processes was changed in day 110-LW compared to day 90-LW fetuses (corresponding to 13% of DEGs). The transcriptional regulator PPARGC1A was predicted to be an important regulator of differentially expressed genes in MS. Fetal blood fructose level, intestinal lactase activity and villous height were the best predicted phenotypic variables with probes mostly involved in lipid metabolism, carbohydrate metabolism and cellular movement biological pathways.ConclusionsCollectively, our findings indicate that the neonatal maturity of pig intestine may rely on functional development of glucose and lipid metabolisms, immune phagocyte differentiation and inflammatory pathways. This process may partially be governed by PPARGC1A.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-4001-2) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

Comparing the intestinal transcriptome of Meishan and Large White piglets during late fetal development reveals genes involved in glucose and lipid metabolism and immunity as valuable clues of intestinal maturity

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Piglets have an accelerated growth rate relative to human infants, and this facilitates shorter-term studies to model infant development, enabling rapid detection of adverse effects of nutritional deficiencies. 49,50 Piglets also can be obtained preterm 53 or at term but small-for-gestational-age, [54][55][56] allowing for investigation of immaturity or intrauterine growth restriction. The piglet is sufficiently large at birth (1.2 kg) to facilitate surgical models, such as short bowel syndrome, 56,57 venous and arterial catheterization, and parenteral support.…”

Section: The Piglet As a Preclinical Biomedical Modelmentioning

confidence: 99%

“…For late-onset sepsis, evidence of moderate quality suggested that oral lactoferrin prophylaxis decreased incidence by 51% (95% CI 0.32-0.73) without adverse effects. For NEC, evidence of low quality suggested that oral lactoferrin prophylaxis decreased NEC stage II or greater by 70% (95% CI 0.12-0.76) without adverse effects 38 To evaluate potential mechanisms, Nguyen et al 115 used a well-established preterm pig model 53,56 to investigate the effects of enteral bLF (10 g/L or 1.2 g/kg/d) on NEC development and inflammation. Contrary to the clinical evidence, they found that the incidence of NEC was similar between piglets fed bLF (60%) and formula alone (62%).…”

Section: Supplementmentioning

confidence: 99%

The Role of Lactoferrin in Gastrointestinal and Immune Development and Function: A Preclinical Perspective

Donovan

2016

The Journal of Pediatrics

View full text Add to dashboard Cite

The early postnatal period is a critical time for gastrointestinal (GI) and immune development. Neonates fed mother's milk have more rapid GI and immune development than fed-formula infants. In addition, clinical and epidemiologic data provide strong evidence that breastfeeding reduces the incidence and/or severity of infectious diseases. Lactoferrin is a 77 kDa, iron-binding glycoprotein that is present at high concentration in human milk compared with bovine milk and infant formula. It is a multifunctional protein that mediates many of the physiological processes in which breastfed infants have advantages over their formula-fed peers, including promoting GI and immune development, protection from infections, and improved cognitive development. Feeding bovine lactoferrin or recombinant human lactoferrin was well tolerated and stimulated intestinal cell proliferation and increased villus length and crypt depth in piglets. Lactoferrin also influenced both systemic and GI immune development by stimulating a balanced T-helper-1/T-helper-2 cytokine immune response. Further, there was a tendency for immune cells to secrete more anti-inflammatory cytokines in an unstimulated state, while being primed for a robust pro-inflammatory response when presented with a bacterial trigger in piglets fed lactoferrin. These findings support clinical studies demonstrating benefits of dietary lactoferrin in the prevention of infections, late onset sepsis, and necrotizing enterocolitis.

show abstract

“…However, preterm piglet models require an extraordinary amount of care, including constant 24‐hour observation and specialized intensive care incubators with environmental controls. Once stabilized, preterm piglets serve as an excellent model for diseases affecting prematurity such as necrotizing enterocolitis 73 , 75 . A natural extension of this model is that preterm pigs may also model the physiological process of intestinal adaptation in preterm human neonates, and as such, preterm piglet models of SBS have emerged 69 , 71 .…”

Section: Emerging Piglet Models Of Neonatal Sbsmentioning

confidence: 99%

Emerging Piglet Models of Neonatal Short Bowel Syndrome

Lim

Turner

Wales

2014

J Parenter Enteral Nutr

View full text Add to dashboard Cite

Short bowel syndrome (SBS) is a growing problem in the human neonatal population. In infants, SBS is the leading cause of intestinal failure, the state of being unable to absorb sufficient nutrients for growth and development. Neonates with SBS are dependent on long-term parenteral nutrition therapy, but many succumb to the complications of sepsis and liver disease. Research in neonatal SBS is challenged by the ethical limits of studying sick human neonates and the heterogeneous nature of the disease process. Outcomes in SBS vary depending on residual intestinal anatomy, intestinal length, patient age, and exposure to nutrition therapies. The neonatal piglet serves as an appropriate translational model of the human neonate because of similarities in gastrointestinal ontogeny, physiological maturity, and adaptive processes. Re-creating the disease process in a piglet model presents a unique opportunity for researchers to discover novel insights and therapies in SBS. Emerging piglet models of neonatal SBS now represent the entire spectrum of disease seen in human infants. This review aims to contextualize these emerging piglet models within the context of SBS as a heterogeneous disease. We first explore the factors that account for SBS heterogeneity and then explore the suitability of the neonatal piglet as an appropriate translational animal model. We then examine differences between the emerging piglet models of neonatal SBS and how these differences affect their translational potential to human neonates with SBS.

show abstract

Dual purpose use of preterm piglets as a model of pediatric GI disease

Cited by 21 publications

References 123 publications

Comparing the intestinal transcriptome of Meishan and Large White piglets during late fetal development reveals genes involved in glucose and lipid metabolism and immunity as valuable clues of intestinal maturity

Comparing the intestinal transcriptome of Meishan and Large White piglets during late fetal development reveals genes involved in glucose and lipid metabolism and immunity as valuable clues of intestinal maturity

The Role of Lactoferrin in Gastrointestinal and Immune Development and Function: A Preclinical Perspective

Emerging Piglet Models of Neonatal Short Bowel Syndrome

Contact Info

Product

Resources

About