Proof of principle study for the development of the world's smallest long-term short bowel syndrome pig model using microminipigs
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Hironori Kudo1, Ryoma Endo1, Eiji Kobayashi2
1Department of Pediatric Surgery, Tohoku University Graduate School of Medicine, Japan.
Background:
This study describes the development of a long-term short bowel syndrome (SBS) model that does not require parenteral nutrition (PN) using Microminipigs (MMP), the smallest experimental pigs, with an adult weight of ≤ 30 kg.
Methods:
Two MMPs were used to establish an SBS model. A 70 % small bowel resection was performed at 6 months of age (body weight, 5 kg), followed by an 85 % resection 4 months later. Untreated MMPs served as controls. Postoperative clinical conditions, weight, blood, and stool samples were monitored longitudinally. Nine months after the initial surgery, the animals were euthanized for organ collection and histological assessments.
Results:
Both treated MMPs remained in good general condition and continued to gain weight postoperatively. Plasma citrulline levels decreased after the second surgery, reflecting a reduced intestinal epithelial mass. At 7 months postoperatively (13 months of age), fecal fat was graded as 2 + in both treated MMPs, whereas the 38-month-old control showed a grade of 0. Histologically, jejunal villi were shorter, and goblet cells were smaller and fewer in the treated MMPs. Colonic crypts were taller in the treated MMPs, with no signs of inflammation or fibrosis in any tissue. Histological examination of the liver revealed no changes in fatty acid levels or fibrosis.
Conclusions:
The MMP SBS model demonstrated prolonged survival and maintained good health for nearly 9 months without PN, which is a significantly longer period than that reported in previous models. This model offers a practical and physiologically relevant platform for future translational and reverse translational studies on intestinal adaptation.
Insights
A novel short bowel syndrome (SBS) model in Microminipigs (MMP) allows long-term survival without parenteral nutrition (PN). This physiologically relevant model aids future intestinal adaptation research.
Area of Science:
- Veterinary Science
- Gastroenterology
- Surgical Research
Background:
- Short bowel syndrome (SBS) poses challenges for long-term patient management.
- Existing animal models often require extensive parenteral nutrition (PN).
- Development of a robust, long-term SBS model without PN is crucial for translational research.
Purpose of the Study:
- To establish a long-term short bowel syndrome (SBS) model in Microminipigs (MMP).
- To assess the feasibility of this model without requiring parenteral nutrition (PN).
- To provide a physiologically relevant platform for studying intestinal adaptation.
Main Methods:
- Two Microminipigs (MMP) underwent staged small bowel resections (70% then 85%).
- Animals were monitored longitudinally for clinical condition, weight, and physiological parameters.
- Histological assessments of intestinal tissues and liver were performed post-euthanasia.
Main Results:
- MMPs survived for 9 months post-surgery without PN, maintaining good health and weight gain.
- Reduced plasma citrulline and increased fecal fat confirmed intestinal insufficiency.
- Histology showed altered jejunal villi and goblet cells, with taller colonic crypts, but no liver pathology.
Conclusions:
- The Microminipig (MMP) SBS model demonstrates prolonged survival without PN, exceeding previous models.
- This model is a practical and physiologically relevant tool for studying intestinal adaptation.
- It facilitates future translational and reverse translational research in SBS and related gastrointestinal disorders.
