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

FASEB J. 2021 Jul;35(7):e21699. doi: 10.1096/fj.202002446RRRR.

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.

Keywords: FUT2; fucosylation; inflammatory bowel disease; intestinal barrier; l-fucose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / chemically induced
  • Colitis / metabolism
  • Colitis / pathology
  • Colitis / prevention & control*
  • Dextran Sulfate / toxicity
  • Epithelial Cells / drug effects*
  • Fucose / pharmacology*
  • Fucosyltransferases / physiology*
  • Galactoside 2-alpha-L-fucosyltransferase
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protective Agents / pharmacology*

Substances

  • Protective Agents
  • Fucose
  • Dextran Sulfate
  • Fucosyltransferases