scholarly journals AN AGE‐DEPENDENT, RESCUABLE DEFECT IN INTESTINAL BARRIER REPAIR IS ASSOCIATED WITH AN IMMATURE ENTERIC GLIAL NETWORK IN A NEONATAL PIG MODEL OF SMALL INTESTINAL STRANGULATING OBSTRUCTION

2021 ◽  
Vol 33 (S12) ◽  
pp. 18-18
Keyword(s):  
Intestinal Barrier ◽  
Pig Model ◽  
Age Dependent ◽  
Neonatal Pig ◽  
Small Intestinal ◽  
Barrier Repair

scholarly journals 4212 An age-dependent, rescuable defect in intestinal barrier repair is associated with an immature enteric glial network in a neonatal pig model of intestinal ischemia

2020 ◽  
Vol 4 (s1) ◽  
pp. 92-93
Author(s):  
Amanda Ziegler ◽  
Anastasia E. Sheridan ◽  
Tiffany A. Pridgen ◽  
Jack Odle ◽  
Laurianne Van Landeghem ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Intestinal Ischemia ◽  
Ex Vivo ◽  
Intestinal Barrier ◽  
Weaned Pigs ◽  
Volume Imaging ◽  
Age Dependent ◽  
Neonatal Pig ◽  
Barrier Repair

OBJECTIVES/GOALS: An age-dependent restitution defect in our neonatal pig intestinal ischemia model is rescued by unknown factors within homogenized mucosa of weaned pigs. A postnatally maturing network of enteric glia regulates the epithelial barrier, so we aim to show rescue is due to replacement of glial factors. METHODS/STUDY POPULATION: Jejunal tissues from suckling or weaned pigs were assessed by RNAseq and processed for immunofluorescent histology and 3-D volume imaging. Jejunal ischemia was surgically induced in weaned pigs and injured mucosa was recovered ex vivo with or without the glial inhibitor fluoroacetate (FA) while monitoring transepithelial electrical resistance (TER). RESULTS/ANTICIPATED RESULTS: Ingenuity Pathways Analysis of RNAseq data revealed significant suppression of numerous pathways critical for epithelial wound healing in suckling pigs (Z-score <−2 for of nine key pathways). Volume imaging studies confirmed lower density (P≤0.05) and complexity of the subepithelial glial network in suckling pigs. Treatment with FA inhibited TER recovery (P<0.0001) and restitution (P<0.05) in weaned pigs, mimicking the suckling pig phenotype and supporting glia as an important regulator of restitution in our model. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings provide important evidence that a developing glial network may be critical to the postnatal development of intestinal barrier repair mechanisms. Ongoing work will explore glial-epithelial interactions in vitro to further define postnatal development of barrier repair.

scholarly journals A breakdown in communication? Understanding the effects of aging on the human small intestine epithelium

2015 ◽  
Vol 129 (7) ◽  
pp. 529-531 ◽  
Author(s):  
Neil A. Mabbott
Keyword(s):  
Small Intestine ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Human Small Intestine ◽  
Small Intestinal ◽  
Effects Of Aging ◽  
Insight Into

A new study by Man and colleagues provides further insight into the effects of aging on small intestinal barrier function in humans. Here, their findings are briefly summarised and the wider implications discussed.

Liver Enzymes Cannot Be Used to Predict Liver Damage after Global Hypoxia-Ischemia in a Neonatal Pig Model

Neonatology ◽  
2009 ◽  
Vol 96 (4) ◽  
pp. 211-218 ◽  
Author(s):  
Mathias Karlsson ◽  
Saulius Satas ◽  
Janet Stone ◽  
Helen Porter ◽  
Marianne Thoresen
Keyword(s):  
Liver Damage ◽  
Liver Enzymes ◽  
Pig Model ◽  
Hypoxia Ischemia ◽  
Neonatal Pig

scholarly journals Intestinal organoids expose heterogeneity in SARS-CoV-2 susceptibility

2021 ◽  
Author(s):  
Kyung Ku Jang ◽  
Maria E Kaczmarek ◽  
Simone Dallari ◽  
Ying-Han Chen ◽  
Jordan Axelrad ◽  
...  
Keyword(s):  
Viral Infections ◽  
Ex Vivo ◽  
Intestinal Barrier ◽  
Infectious Agents ◽  
Interferon Signature ◽  
Interindividual Differences ◽  
Intestinal Organoids ◽  
Small Intestinal ◽  
Substantial Heterogeneity ◽  
Primary Tissue

Organoids generated from primary human specimens facilitate investigation of the intestinal barrier by recreating the complex cellular composition of the epithelium. Although the significance remains unclear, intestinal organoid lines display heterogeneity in their growth and morphology. We hypothesized that organoids will also display variability in the degree to which they are susceptible to infectious agents. Using SARS-CoV-2 as a model, we found orders of magnitude differences in the amount of SARS-CoV-2 recovered from small intestinal and colonic organoids generated from different donors. SARS-CoV-2 burden did not correlate with demographic or clinical features associated with donors, but rather reflected the expression level of the virus receptor ACE2. Remarkably, organoid ACE2 transcript levels matched the amount of ACE2 detected in primary tissue from the same individual, indicating that certain properties of the intestinal epithelium are retained during ex vivo differentiation. Longitudinal transcriptomics of organoids identified a delayed yet robust interferon signature, the magnitude of which corresponded to the degree of SARS-CoV-2 infection. These results suggest that intestinal organoids display substantial heterogeneity in their ability to support viral infections and can potentially inform mechanisms behind interindividual differences in susceptibility to infectious disease.

Effects of graded levels of xylo-oligosaccharides on growth performance, serum parameters, intestinal morphology and intestinal barrier function in weaned piglets

2021 ◽  
Author(s):  
Yuxia Chen ◽  
Yining Xie ◽  
Ruqing Zhong ◽  
Hui Han ◽  
Lei Liu ◽  
...  
Keyword(s):  
Growth Performance ◽  
Intestinal Barrier ◽  
Intestinal Morphology ◽  
Intestinal Barrier Function ◽  
Weaned Piglets ◽  
Villus Height ◽  
Expression Levels ◽  
Small Intestinal ◽  
Dietary Treatments ◽  
Mrna Expression Levels

Abstract The objective of this study was to investigate the effects of xylo-oligosaccharides (XOS) supplementation on growth performance, serum parameters, small intestinal morphology, intestinal mucosal integrity, and immune function in weaned piglets. A total of 240 weaned piglets with an average body weight (BW) of 8.82 ± 0.05 kg (28 d of age) were assigned randomly to 4 dietary treatments in a 28-d trial, including a control diet (CON), 3 diets with XOS supplementation at the concentration of 100, 500 and 1000 mg/kg (XOS100, XOS500, and XOS1000). There were 4 replicates per treatment with 15 pigs per pen. From d 1 to 14, there were no differences (P &gt; 0.05) in average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G:F) during the different treatments. The different doses of XOS showed a quadratic effect on BW on d 28, ADG and G:F d 1-28 of piglets (P &lt; 0.05). From d 15 to 28, ADG of pigs fed the XOS500 diet was higher (P &lt; 0.05) than pigs fed the CON diet. During the overall period (d 1 to 28), pigs fed the XOS500 diet had a higher BW, ADG and G:F than pigs fed the CON diet (P &lt; 0.05). In addition, compared with the CON group, the XOS500 group had significantly higher serum total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD) and catalase (CAT) levels and lower malondialdehyde (MDA) levels on d 14 and 28 (P &lt; 0.05). The serum immunoglobulin G (IgG) concentration in the XOS500 group was also significantly higher compared with the CON group on d 14 and 28 (P &lt;0.05). However, serum immunoglobulin A (IgA) and immunoglobulin M (IgM) were not affected by the dietary treatments. Supplementation of XOS500 to the feed significantly increased the villus height (VH) and villus height to crypt depth ratio (VH:CD) in the jejunum and ileum in comparison with the CON and XOS1000 group. Moreover, the XOS500 group significantly elevated the expression levels of Occludin and zonula occludens protein-1 (ZO-1) in the ileum compared to the CON group. The ileal interleukin (IL)-1β, IL-8 and interferon (IFN)-γ mRNA expression levels in the XOS100 and XOS500 group were markedly lower than in the CON group. In contrast, the ileal IL-10 mRNA expression levels were remarkably higher in the XOS500 than CON group. In conclusion, xylo-oligosaccharides have a beneficial effect on growth performance by improving serum antioxidant defense system, serum IgG, small intestinal structure and intestinal barrier function in weaned piglets.

Region-specific ontogeny of α-2,6-sialyltransferase during normal and cortisone-induced maturation in mouse intestine

2002 ◽  
Vol 282 (3) ◽  
pp. G480-G490 ◽  
Author(s):  
Dingwei Dai ◽  
N. Nanda Nanthakumar ◽  
Tor C. Savidge ◽  
David S. Newburg ◽  
W. Allan Walker
Keyword(s):  
Large Intestine ◽  
Regional Differences ◽  
Trophic Factors ◽  
Mrna Levels ◽  
Age Dependent ◽  
Regional Specificity ◽  
Microvillus Membrane ◽  
Mouse Intestine ◽  
Small Intestinal ◽  
Small And Large Intestine

Regional differences in the ontogeny of mouse intestinal α-2,6-sialyltransferase activities (α-2,6-ST) and the influence of cortisone acetate (CA) on this expression were determined. High ST activity and α-2,6-ST mRNA levels were detected in immature small and large intestine, with activity increasing distally from the duodenum. As the mice matured, ST activity (predominantly α-2,6-ST) in the small intestine decreased rapidly to adult levels by the fourth postnatal week. CA precociously accelerated this region-specific ontogenic decline. A similar decline of ST mRNA levels reflected ST activity in the small, but not the large, intestine. Small intestinal sialyl α-2,6-linked glycoconjugates displayed similar developmental and CA induced-precocious declines when probed using Sambucus nigraagglutinin (SNA) lectin. SNA labeling demonstrated age-dependent diminished sialyl α2,6 glycoconjugate expression in goblet cells in the small (but not large) intestine, but no such regional specificity was apparent in microvillus membrane. This suggests differential regulation of sialyl α-2,6 glycoconjugates in absorptive vs. globlet cells. These age-dependent and region-specific differences in sialyl α-2,6 glycoconjugates may be mediated in part by altered α-2,6-ST gene expression regulated by trophic factors such as glucocorticoids.

Whole body hypothermia using a portable cooling unit in a neonatal pig model: Implications for transport

2010 ◽  
Vol 3 (1) ◽  
pp. 15-20
Author(s):  
Eric Rabenstein ◽  
Melissa Tyree ◽  
Daniel Dirnberger ◽  
Robert DiGeronimo
Keyword(s):  
Pig Model ◽  
Whole Body ◽  
Cooling Unit ◽  
Neonatal Pig

scholarly journals Small intestinal MUC2 synthesis in human preterm infants

2009 ◽  
Vol 296 (5) ◽  
pp. G1085-G1090 ◽  
Author(s):  
Maaike W. Schaart ◽  
Adrianus C. J. M. de Bruijn ◽  
Henk Schierbeek ◽  
Dick Tibboel ◽  
Ingrid B. Renes ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Isotopic Ratio ◽  
Periodic Acid ◽  
Gel Filtration ◽  
Intestinal Barrier ◽  
Cesium Chloride ◽  
Intestinal Barrier Function ◽  
Synthesis Rate ◽  
Periodic Acid Schiff ◽  
Small Intestinal

Mucin 2 (MUC2) is the structural component of the intestinal protective mucus layer, which contains high amounts of threonine in its peptide backbone. MUC2 synthesis rate might be a potential parameter for intestinal barrier function. In this study, we aimed to determine whether systemic threonine was used for small intestinal MUC2 synthesis and to calculate the MUC2 fractional synthetic rate (FSR) in human preterm infants. Seven preterm infants with an enterostomy following bowel resection for necrotizing enterocolitis received intravenous infusion of [U-13C]threonine to determine incorporation of systemic threonine into secreted MUC2 in intestinal outflow fluid. Small intestinal MUC2 was isolated using cesium chloride gradient ultracentrifugation and gravity gel filtration chromatography. MUC2-containing fractions were identified by SDS-PAGE/periodic acid-Schiff staining and Western blot analysis and were subsequently pooled. Isotopic enrichment of threonine, measured in MUC2 using gas chromatography isotopic ratio mass spectrometry, was used to calculate the FSR of MUC2. Systemically derived threonine was indeed incorporated into small intestinal MUC2. Median FSR of small intestinal MUC2 was 67.2 (44.3–103.9)% per day. Systemic threonine is rapidly incorporated into MUC2 in the small intestine of preterm infants, and thereby MUC2 has a very high synthesis rate.

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