PP260 - FGF2 ENHANCES INTESTINAL REPAIR AND POTENTIALLY IMPROVES NUTRIENT ABSORPTION IN DSS-INDUCED COLITIS VIA ACTIVATION OF THE FGFR1/WNT SIGNALING PATHWAY

PP260

FGF2 ENHANCES INTESTINAL REPAIR AND POTENTIALLY IMPROVES NUTRIENT ABSORPTION IN DSS-INDUCED COLITIS VIA ACTIVATION OF THE FGFR1/WNT SIGNALING PATHWAY

Q. Tian¹, H. Li¹, Z. Huang¹, B. Zhu¹, Y. Chen¹, M. He¹, W. Sun^1,*

¹The First Affiliated Hospital of Wenzhou Medical University,, Wenzhou, China

Rationale: Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation, epithelial barrier disruption, and subsequent malnutrition. While mucosal healing is a key therapeutic goal, strategies that directly and functionally link epithelial repair to the restoration of nutrient absorption are lacking. FGF2 is implicated in tissue repair, but its potential to improve nutritional outcomes in IBD via downstream functional reprogramming of the epithelium remains unexplored.

Methods: Mice were treated with FGF2 (1.0 mg/kg). Disease activity was assessed via the DAI, colon length, and histology. Nutrient absorption was assessed by tracking serum appearance of orally gavaged stable isotope-labeled glucose and leucine. Single-cell RNA sequencing was processed using the 10x Genomics. Serum metabolomics were performed using LC-MS. 

Results: FGF2 treatment significantly ameliorated colitis severity. It restored barrier function, reducing serum FITC-dextran and enhancing the absorption rate of labeled nutrients. scRNA-seq revealed that DSS injury depleted absorptive enterocytes and goblet cells, while FGF2 treatment reversed this shift. This enterocyte population exhibited a marked upregulation of genes involved in nutrient transport. Metabolomic profiling showed that FGF2 treatment partially increased levels of essential amino acids. Mechanistically, FGF2 activated the WNT/β-catenin pathway. This activation was necessary and sufficient for FGF2-induced upregulation of key nutrient transporters and the enhancement of barrier function. Chromatin immunoprecipitation confirmed increased β-catenin binding to the promoters of SGLT1 and PepT1.

Conclusion: The FGF2/FGFR1 axis emerges as a key integrator of epithelial regeneration and nutritional recovery, representing a novel therapeutic target to concurrently combat mucosal damage and malnutrition in IBD.

Disclosure of Interest: None declared