The hidden piece in inflammatory bowel diseases: The significance of intestinal mucus in mediating the bacteria-cells crosstalk

Inflammatory bowels diseases (IBD) are chronic conditions with a complex not yet fully understood pathogenesis, characterized by a compromised intestinal barrier. Traditionally, the gut microbiota and the intestinal epithelium have been considered the primary contributors to this dysfunction. However, emerging evidence underscore the crucial role of a third key player: the intestinal mucus. Mucus acts as an equal partner alongside the epithelium and microbiota, functioning as a cell-free interface that filters molecules and toxins while preventing bacterial penetration through its unique structural and compositional properties. Despite its significance, the role of mucus in IBD remains underappreciated, with relative few studies focusing specifically on mucus compared to ones centred on epithelial cells and bacteria. This review explores the features of the intestinal barrier by exanimating each component of the gut mucosa (<i>i.e.</i>, epithelium, microbiota, and mucus) from a mucus-centred perspective. In this way, we aim to highlight the crucial role of mucus in IBD and its importance for new potential therapeutic treatments.