ABSTRACT Neonatal short bowel syndrome (SBS) often leads to intestinal failure and dependence on parenteral nutrition (PN). Given the role of liver X receptor (LXR) activation in lipid metabolism and mucosal repair, this study was designed to examine the effects of LXR agonist GW3965 on early adaptive responses in neonatal piglets with SBS. Seven-day-old Bama mini-piglets underwent 75% jejunoileal resection and were randomized into a control group (n = 6) and a GW3965-treated group (n = 4; 2 mg/kg/day administered via jugular vein). The effects of GW3965 on post-resection intestinal responses and key molecular pathways were investigated using a combination of in vivo (piglets) and in vitro (human intestinal organoid) models. Administration of the LXR agonist GW3965 promoted significant improvements in gut barrier integrity and mucosal structure in the TPN-supported SBR piglet model during the 7-day postoperative period. GW3965 significantly increased villus height in the jejunum and ileum (both p in vitro studies confirmed that GW3965 directly stimulated the growth of human intestinal organoids. Notably, GW3965 altered colonic gene expression, upregulating markers typically associated with ileal identity. These findings suggest that targeting the LXR pathway may hold therapeutic potential for augmenting the intestinal regeneration.
Feng et al. (Fri,) studied this question.