Colonic Epithelial-derived FGF1 Protects against Inflammatory Bowel Disease via Driving Intestinal Stem Cells Differentiation toward Goblet Cells

Inflammatory bowel disease (IBD), characterized by impaired intestinal epithelia barrier, especially goblet cell loss, lacks effective treatment strategies. FGF1, the most abundantly expressed FGF ligand in the colon, was significantly downregulated in IBD mouse models and patients. However, the role of FGF1 in the pathogenesis of IBD, particularly in goblet cell loss, remains elusive. The effects of intestinal epithelial cells (IECs)-specific deletion of Fgf1 and recombinant FGF1 (rFGF1) supplementation on colonic epithelial barrier, cellular composition, and disease phenotypes in IBD mice were investigated. In vitro colonic organoids were used to analyze the effect of FGF1 on the lineage commitment of intestinal stem cells (ISCs). RNA sequencing, shRNA, and Villin-CreERT2Atoh1fl/fl and Lgr5-EGFP-CreERT2Fgfr2fl/fl mice were used to explore the molecular mechanisms by which FGF1 drives ISCs differentiation toward goblet cells.