Proof of principle study for the development of the world’s smallest long-term short bowel syndrome pig model using microminipigs

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.