Massive Small Bowel Resection Induces IFALD-Like Liver Injury in Mice.

Background: Severe short bowel syndrome (SBS) frequently leads to intestinal failure-associated liver disease (IFALD); nonetheless, the mechanisms underlying early hepatic changes remain unclear. Existing SBS rodent models involving ≥ 90% small bowel resection often exhibit high postoperative mortality, limiting the ability to evaluate subacute liver injury independent of parenteral nutrition. Methods: We established a severe SBS murine model by performing 90% small bowel resection (SBS90) in young C57BL/6 mice using a standardized Albert-Lembert anastomotic technique and optimized perioperative management, allowing survival to postoperative day (POD) 14 or longer without parenteral nutrition. Serum biochemistry and liver histology were compared between the Sham, SBS50 (SBS murine model by performing 50% small bowel resection), SBS75 (SBS murine model by performing 75% small bowel resection), and SBS90 groups. Results: SBS90 mice exhibited significantly higher serum ALT and T-bil levels than did controls. At POD14, the liver histology demonstrated macrovesicular steatosis with minimal inflammatory infiltration, whereas SBS90 mice evaluated on POD28 exhibited macrovesicular steatosis together with severe portal and periportal inflammatory cell infiltration. Conclusion: This reproducible severe SBS mouse model enabled early and time-dependent hepatic injury evaluation following massive intestinal resection, providing a platform for studying IFALD-contributing mechanisms.