The dietary fibre rhamnogalacturonan improves intestinal epithelial barrier function in a microbiota-independent manner.

Background And Purpose: Dietary fibre comprises a complex group of polysaccharides that are indigestible but are fermented by gut microbiota, promoting beneficial effects to the intestinal mucosa indirectly through the production of short chain fatty acids. We found that a polysaccharide, rhamnogalacturonan (RGal), from the plant Acmella oleracea, has direct effects on intestinal epithelial barrier function. Our objective was to determine the mechanism whereby RGal enhances epithelial barrier function.

NRG4-ErbB4 signaling represses proinflammatory macrophage activity.

Proinflammatory macrophages are essential drivers of colitis and express the growth factor receptor ErbB4. This study tested the role of ErbB4 and its specific ligand, NRG4, in regulating macrophage function. We show that endogenous NRG4-ErbB4 signaling limits macrophage production of proinflammatory cytokines in vitro and limits colitis severity in vivo and thus is a potential target for therapeutic intervention.

Signaling pathways induced by serine proteases to increase intestinal epithelial barrier function.

Changes in barrier function of the gastrointestinal tract are thought to contribute to the inflammatory bowel diseases Crohn's disease and ulcerative colitis. Previous work in our lab demonstrated that apical exposure of intestinal epithelial cell lines to serine proteases results in an increase in transepithelial electrical resistance (TER). However, the underlying mechanisms governing this response are unclear.

The serine protease-mediated increase in intestinal epithelial barrier function is dependent on occludin and requires an intact tight junction.

Barrier dysfunction is a characteristic of the inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. Understanding how the tight junction is modified to maintain barrier function may provide avenues for treatment of IBD. We have previously shown that the apical addition of serine proteases to intestinal epithelial cell lines causes a rapid and sustained increase in transepithelial electrical resistance (TER), but the mechanisms are unknown.