Development and validation of an ambulatory piglet model for short bowel syndrome with ileo-colonic anastomosis

Abstract

Short bowel syndrome is associated with significant comorbidities and mortality. This study is important as unlike current systems, it provides a validated piglet model which mirrors anatomical, histological, and serological characteristics observed in human SBS. This model can be used to advance knowledge into mechanistic pathways and therapeutic modalities to improve outcomes for SBS patients. This study is novel in that in addition to significant reduction in the remnant bowel and noted liver disease, we also developed a method to emulate ileocecal valve resection and described gut adaptive responses which has important clinical implications in humans.

Keywords: Short bowel syndrome; animal model; bowel resection; ileocecal valve resection; intestinal failure; intestinal failure-associated liver disease; piglet model.

Figure 1.

SBS with ileo-colonic anastomosis: (a) Unresected ileo-colonic junction. (b) Electrocautery is used to obliterate the mesentery to accomplish the resection. Noted here is post resection ileo-colonic anastomosis. (c) Intact anastomosis noted at animal sacrifice. (A color version of this figure is available in the online journal.)

Figure 2.

Weight gain: (a) Daily weight gain for animals in each group. (b) Absolute change in weight from Day 0 to Day 14 of the study. Note no differences in weight gain between EN, TPN, or SBS.

Figure 3.

Serum markers: (a) Conjugated bilirubin, (b) GGT, (c) bile acids. Note: Significant increase in serum bilirubin, GGT, and bile acids in TPN and SBS groups vs. EN. Both bilirubin and GGT was also higher in SBS vs. TPN. Each column reflects the mean for that group. Error bars represent standard error. Differences between groups are based on the T test. All tests were two-sided using a significance level of 0.05.

Figure 4.

Linear gut density: (a) Proximal and distal gut segments. Note: Significant reduction in proximal and distal linear gut density (g/cm) in TPN and SBS group vs. EN. SBS linear gut density was higher than TPN for the proximal bowel. (b) Gut adaptation in SBS. Note that the D0 segment (proximal end of the resection) adapted over 14 days – D14 in SBS animals. Each column reflects the mean for that group. Error bars represent standard error. Differences between groups are based on the T test. All tests were two-sided using a significance level of 0.05.

Figure 5.

Small bowel histology (200× magnification): EN, TPN, and SBS groups. Note villous atrophy (arrows) in TPN and SBS animals in comparison to EN animals. (A color version of this figure is available in the online journal.)

Figure 6.

(a) mRNA expression for gut FXR, gut FGF19, and Hepatic CyP7A1. Note a significant fold reduction in both gut FXR and gut FGF19 in the TPN and SBS group vs. the EN group. CyP7A1 was much higher in TPN and SBS against the EN controls. Each column reflects the mean for that group. Error bars represent standard error. Differences between groups are based on the T test. All tests were two-sided using a significance level of 0.05.