PSIX-25 Porcine epidemic diarrhea virus infection impairs intestinal nutrient transport in piglets

Porcine epidemic diarrhea virus (PEDV) infection can occur in all ages of pigs, but neonatal piglets are the most susceptible and sensitive to the virus. PEDV infection can cause intestinal dysfunction, severe diarrhea and even death in piglets. This study determined the effects of PEDV infection on the absorptive function and gene expression of nutrient transporters in the small intestine of piglets by microarray assay. Sixteen 7-day-old healthy piglets fed with milk replacer and were randomly allocated to one of two treatments (the Control and PEDV groups). After a 5-day adaptation period, piglets (n = 8) were orally administrated with either sterile saline or PEDV (Yunnan province strain) solution at 104.5TCID50 (50% tissue culture infectious dose) per piglet. On day 5 of the trial, D-xylose (0.1 g/kg BW) was orally administrated to all piglets. One hour later, jugular vein blood samples were collected, and then all piglets were killed to obtain the intestinal samples. Compared with the control, PEDV infection increased (P < 0.05) incidence of diarrhea, plasma DAO activity and iFABP level, while decreased (P < 0.05) plasma D-xylose concentration of piglets. Moreover, PEDV infection altered the amino acids profiles (P < 0.05), and decreased (P < 0.05) the gene expression of AQPs (AQP4, AQP8 and AQP10), amino acids transporters (y+LAT1, b0’+AT, and PepT1), molecules associated with lipid transport and metabolism (LPL, SLC27A2, and ACSL3), and glucose transport and metabolism (GLUT2 and INSR). However, PEDV infection enhanced (P < 0.05) the gene epression of PCK1, ASS1, SGLT1, and CFTR in the jejunum of piglets. Collectively, these comprehensive results indicate that PEDV infection impairs intestinal absorptive function and inhibits the expression of genes associated with nutrient transport and metabolism in piglets.

Lifor Solution: An Alternative Preservation Solution in Small Bowel Transplantation

Background and Objectives. The intestinal mucosa is extremely sensitive to ischemia. Better intestinal preservation is the first step to improve the results of intestinal transplantation. The aim of the study is to investigate the effect of cold Lifor solution on preservation of swine small bowel.Methods. Swine ileum segments (200 cm) were allotransplanted heterotopically after 9-hour cold storage with UW solution (group 1,n=6), with Lifor solution (group 2,n=6), or without storage (group 3,n=6), respectively. After cold storage, mucosal adenosine triphosphate (ATP) concentrations and histopathologic analysis after preservation were performed. At day 7 after the transplantation, intestinal absorptive function was also observed.Results. After 9 h cold preservation, pathological changes, the content of ATP in the intestinal mucosa, and the intestinal absorptive function after transplantation in group 2 were similar to those of group 1.Conclusion. The effect of cold storage of swine small bowel with Lifor solution is similar to that of UW solution. It may provide additional rationale for further exploration of Lifor as an alternative preservation solution in small bowel transplantation.

Stimulation of intestinal growth and function with DPP4 inhibition in a mouse short bowel syndrome model

Glucagon-like peptide-2 (GLP-2) has been shown to be effective in patients with short bowel syndrome (SBS), but it is rapidly inactivated by dipeptidyl peptidase IV (DPP4). We used an orally active DPP4 inhibitor (DPP4-I), MK-0626, to determine the efficacy of this approach to promote adaptation after SBS, determined optimal dosing, and identified further functional actions in a mouse model of SBS. Ten-week-old mice underwent a 50% proximal small bowel resection. Dose optimization was determined over a 3-day post-small bowel resection period. The established optimal dose was given for 7, 30, and 90 days and for 7 days followed by a 23-day washout period. Adaptive response was assessed by morphology, intestinal epithelial cell (IEC) proliferation (proliferating cell nuclear antigen), epithelial barrier function (transepithelial resistance), RT-PCR for intestinal transport proteins and GLP-2 receptor, IGF type 1 receptor, and GLP-2 plasma levels. Glucose-stimulated sodium transport was assessed for intestinal absorptive function. Seven days of DPP4-I treatment facilitated an increase in GLP-2 receptor levels, intestinal growth, and IEC proliferation. Treatment led to differential effects over time, with greater absorptive function at early time points and enhanced proliferation at later time points. Interestingly, adaptation continued in the group treated for 7 days followed by a 23-day washout. DPP4-I enhanced IEC proliferative action up to 90 days postresection, but this action seemed to peak by 30 days, as did GLP-2 plasma levels. Thus DPP4-I treatment may prove to be a viable option for accelerating intestinal adaptation with SBS.