Developing a Novel Ambulatory Total Parenteral Nutrition-Dependent Short Bowel Syndrome Animal Model

Abstract

Background: Short bowel syndrome (SBS) results from extensive bowel resection. Patients with SBS require total parenteral nutrition (TPN) for survival. Understanding mechanisms contributing to TPN-associated liver injury and gut atrophy are critical in developing SBS therapies. Existing SBS models using tethered animals have significant limitations and are unlike ambulatory human SBS patients. We hypothesized that we could induce SBS in piglets and develop an ambulatory TPN-SBS model.

Material and methods: Eighteen neonatal pigs received duodenal and jugular catheters. They were fitted with a jacket holding TPN and a miniaturized pump. Six piglets had 90% small bowel resection and catheter placement (SBS group). Non-SBS piglets were randomized into enteral nutrition (EN) or TPN.

Results: Bowel resection was successfully accomplished in SBS animals. Weight gain was similar in all groups. SBS animals had increased serum bilirubin compared to EN. Mean conjugated bilirubin ± SD was 0.045 ± 0.01 for EN, (P = 0.03 EN versus TPN and P = 0.03 SBS versus EN) and 1.09 ± 1.25 for TPN, (P = 0.62 TPN versus SBS). Gut density was reduced in the TPN group compared to EN and SBS groups. Mean gut density ± SD was 0.11 ± 0.04 for TPN (P = 0.0004 TPN versus SBS and P = 0.00007 TPN versus EN) and not statistically different for EN versus SBS (P = 0.32).

Conclusions: We created a novel, ambulatory TPN-SBS model using piglets, mimicking long-term TPN delivery in human SBS patients. Our model demonstrated TPN-related conjugated hyperbilirubinemia and compensatory gut hypertrophy, as noted in humans with SBS. This model holds great potential for future research.

Keywords: Ambulatory; Animal; Cholestasis; Gut atrophy; Model; Short bowel syndrome; TPN.

Figure 1:

(A) Electrocautery is used to obliterate the mesentery to accomplish the resection. (B) Resected bowel is measured to confirm 90% resection. (C) Jejuno-ileal side to side stapled anastomosis (Just Right® 5 mm Stapler)

Figure 2:

(A) Intact anastomosis on serosal surface (arrow marks staples). (B) Anastomosis has been divided, intact mucosa is visualized.

Figure 3:

Daily weight gain in each group. Each column reflects the mean for that group. Error bars represent standard error. Differences between groups are based on the T test. All test were 2 sided using a significance level of 0.05. Note: No difference in daily weight gain between the groups.

Figure 4

(A): Serum conjugated bilirubin. Each column reflects the mean for that group. Error bars represent standard error. Differences between groups are based on the T test. All test were 2 sided using a significance level of 0.05. Note: Significant elevation of bilirubin in the TPN and SBS group vs EN. No statistical differences in serum bilirubin were noted between TPN and SBS. (B) Gut density as measured in grams per centimeter. Each column reflects the mean for that group. Error bars represent standard error. Differences between groups are based on the T test. All test were 2 sided using a significance level of 0.05. Note: Significant reduction of gut density with TPN vs EN. SBS had the highest gut density, likely secondary to gut adaptation.