Mucoprotectants and gut barrier: mechanisms of action and clinical applications in IBS. Is there a possible role?

Abstract

Impaired gut barrier function plays a pivotal role in the pathophysiology of irritable bowel syndrome (IBS), particularly in IBS with diarrhea. Mucoprotectants, such as xyloglucan, gelatin tannate and pea protein tannins, offer a novel therapeutic approach by restoring intestinal permeability and reducing inflammation. This review assesses preclinical and clinical evidence supporting mucoprotectants in IBS with diarrhea management. Preclinical studies indicate their efficacy in reducing intestinal permeability and inflammation, while clinical trials demonstrate improvements in stool consistency, abdominal pain and bloating. Despite these promising results, comparative studies are needed to establish the superiority of specific mucoprotectants and their optimal use in clinical practice.

Keywords: IBS-D; gelatin tannate; gut barrier function; intestinal permeability; irritable bowel syndrome; mucoprotectants; xyloglucan.

FIGURE 1

Schematic representation of the intestinal barrier and mechanism of action of mucoprotectants. The intestinal barrier comprises the mucus layer, the intestinal–epithelial barrier and the gut–vascular barrier. The mucus layer prevents the adhesion of pathogenic organisms to the epithelium. The intestinal–epithelial barrier consists of an enterocyte monolayer joined together by the junctional complex (i.e., tight junctions, adherens junctions, gap junctions and desmosomes) that maintains barrier integrity and regulates the paracellular trafficking of solutes and fluids. Molecules can cross the intestinal–epithelial monolayer also through the cells (transcellular route). The gut vascular barrier regulates the translocation of intestinal content into the systemic circulation and, in turn, into organs far from the intestine. It includes endothelial cells and enteric neurons placed in the lamina propria, where are also present innate immune cells (i.e., dendritic cells, macrophages and lymphoid cells). When the mucus layer is impaired, access by pathogens, toxins and allergens across the intestinal barrier is granted, which may enhance immune-inflammatory responses. This response, in turn, may lead to further distortion of intestinal permeability and perpetuation of mucosal low-grade inflammation, leading to visceral hypersensitivity. Mucoprotectants share mucoadhesive properties and the ability to create a film-forming barrier over the intestinal mucosa or protect the mucus layer, helping to restore gut permeability and avoid or decrease mucosal inflammation, reducing the effect of noxious agents on the intestinal barrier.