Undissociated gelatine tannate and xyloglucan prevent gut leakiness and mucosal inflammation induced by LPS: insights in the mechanism of action.

UEG journal. October 2016. Vol 4. Suppl. 1 Pag A651

Introduction:

Gelatine tannate (GT) and xylogucan (XG) are commercially available in several countries for the oral treatment of diarrhea in children and adults. However, the mechanism of action remains poorly understood.

Aims & Methods:

Therefore, we aimed to investigate the effects of GT and XG treatment and the mechanisms of action involved in LPS treated rats, an animal model characterized by two common gastroenteritis features, namely the intestinal epithelial barrier impairment and mucosal inflammation. The parameters evaluated were 1) the severity of intestinal mucosal inflammation, 2) gut paracellular permeability, 3) tight junction proteins expression and 4) spatial localization of the commensal bacteria load in ileal and colonic sections. Male Wistar rats were orally treated with GT (250 mg/kg) or XG (12.5 mg/kg) or vehicle (water plus Na2CO3, p.o) 2 h before IP injection of LPS from E. coli (1 mg/kg). Jejunal tissue strips were collected to evaluate 1) mucosal inflammation by MPO activity measurement 2) paracellular intestinal permeability to FITC-dextran 4 KDa in Ussing chambers and 3) occudin and Jam-A protein expression levels by western blotting. The commensal bacterial load was determined by FISH technique in ileal and colonic samples.

Results:

Compared with control, LPS administration promotes a significant increase (p5 0.05) of intestinal paracellular permeability associated with a decreased expression of occludin and JAM-A and a subsequent jejunal mucosal inflammation. LPS also induced mucus barrier impairment reflected by the close apposition of commensal bacteria to ileal and colonic epithelium. Both GT and XG significantly (p5 0.05) reduce the severity of LPS induced mucosal inflammation and jejunal hyperpermeability. However, both treatments did not prevent the LPS-induced occludin and JAM-A down regulation. Further, GT and XG treatments result to a containment of the commensal bacterial load at the external face of the mucus layer limiting the bacterial mucus layer invasion and contact between bacteria and intestinal epithelium.

Conclusion:

In this study we show that GT and XG treatments prevent LPS induced gut leakiness and subsequent intestinal inflammation. These beneficial effects result from a mechanical protection of the gut epithelium through a ‘‘coat’’-forming ability which avoids the upload of adverse luminal factors through the intestinal epithelium and subsequent adverse consequences.