Translational evaluation of Gelsectan® effects on gut barrier dysfunction and visceral pain in animal models and irritable bowel syndrome with diarrhoea

Background: Gelsectan (R) is a formulation of xyloglucan (XG), pea protein, grape seed extract (PPGS) and xylo-oligosaccharides (XOS). Our aim was to examine the effect of Gelsectan (R) on rectal sensitivity in an animal model, abdominal pain in irritable bowel syndrome with diarrhoea (IBS-D) subjects and intestinal permeability in both conditions. Methods: Animals: Wistar rats received gavage with XOS, XG + PPGS or XG + PPGS + XOS, as a single dose or for 7 days before a partial restraint stress (PRS). Visceromotor response to rectal distension and total gut paracellular permeability to 51Cr-EDTA were assessed. Humans: IBS-D and control patients were involved. After initial colonoscopy with biopsy sampling Gelsectan (R) was administered to IBS-D patients for 12 weeks. Stool count and pain scores were documented. After treatment, colonoscopy was repeated. The permeability of biopsy samples was measured in Ussing-chambers. Adherent mucus layer, Muc-2 expression as well as TNF alpha, Interferon IFN gamma were evaluated by histology/immunohistochemistry and ELISA assays, respectively. Results: Animal studies: In control rats, PRS significantly increased visceromotor response as well as gut paracellular permeability. Single dose administration of XG + PPGS + XOS failed to reverse PRS, but 7 days of oral treatment reversed PRS-induced rectal hypersensitivity and gut hyperpermeability. Human studies: Gelsectan (R) treatment significantly reduced and abdominal pain. Intestinal permeability in IBS-D patients was elevated compared with controls, Gelsectan (R) restored permeability in the ascendent colon. Periodic acid-Schiff-stained mucus layer was significantly thinner in IBS-D patients compared with controls, In both segments, mucus thickness and the proportion of Muc-2 positive cells were not affected by Gelsectan (R) treatment. IFN gamma tissue level in the sigmoid colon shows modest mucosal inflammation in IBS-D. Conclusions: Gelsectan (R) prevented rectal hypersensitivity in rats, abdominal pain in human and intestinal hyperpermeability in rat and human studies respectively. These effects involve restoration of gut permeability. Based on this translational study, Gelsectan (R) can be considered as an effective therapy for IBS-D symptoms. image