Exogenous l ‐fucose protects the intestinal mucosal barrier depending on upregulation of FUT2‐mediated fucosylation of intestinal epithelial cells

Abstract FUT2, a protein that uses l ‐fucose to mediate fucosylation of intestinal epithelial cells, is one of the detected gene variants in IBD patients. We aimed to investigate whether exogenous l ‐fucose could be an enteral nutritional supplement to protect intestinal barrier function. The effect of l ‐fucose on the restoration of epithelial barrier function in both the DSS‐induced colitis mouse model and LPS‐stimulated Caco‐2 cells was investigated, and the impact on fucosylation of epithelial cells was examined. The severity of DSS‐induced colitis was significantly reduced by l ‐fucose. Restoration of epithelial barrier function by l ‐fucose was detected. Direct l ‐fucose‐mediated protection of tight junctions was observed in Caco‐2 cells. Moreover, exogenous l ‐fucose promoted the exogenous metabolic pathway of l ‐fucose, and fucosylation of epithelial cells both in vivo and in vitro. Moreover, knockout of the FUT2 gene restrained fucosylation and the protective effect of l ‐fucose on barrier function. The severity of colitis was not improved by l ‐fucose in Fut2 knockout mice. Therefore we conclude that exogenous l ‐fucose protects intestinal barrier function and relieves intestinal inflammation via upregulation of FUT2‐mediated fucosylation of intestinal epithelial cells.