At the IBS Days meeting in Bologna, Nathalie Vergnolle (Inserm, France) discussed the potential role of proteases in altering the intestinal mucus layer in irritable bowel syndrome (IBS). Several proteases are overexpressed or released at increased levels in patients with IBS. These enzymes may originate from the intestinal microbiota or from host epithelial cells, placing the mucus barrier directly at the interface of their activity.

Experimental studies indicate that specific proteases contribute to normal mucus processing, but their dysregulation could promote excessive mucus degradation and compromise barrier function. Microbial proteases produced by several bacterial species have been associated with mucus degradation, although most available studies have not directly examined the human intestinal mucus layer in IBS. Host-derived proteases may also be involved. Thrombin, for example, has been shown to degrade mucus, while the effects of epithelial trypsin isoforms remain to be clarified. Elastase, another epithelial protease, is also upregulated in patients with IBS and represents a potential contributor to mucus disruption.

Further studies are needed to characterize the composition, organization and spatial distribution of intestinal mucus in patients with IBS. This remains technically challenging because bowel preparation and conventional biopsy processing can impair mucus preservation. Future research should also identify the microbial and epithelial proteases that act directly on human intestinal mucus and determine whether protease-producing microorganisms are enriched in IBS. Addressing these questions could clarify the contribution of mucus barrier alterations to IBS pathophysiology and reveal new therapeutic targets.