Intestinal bacteria are usually regarded as harmless commensals in healthy intestine but are pathogens, if these invade the tissues. The mucus gel separates the luminal bacteria from the epithelial surface throughout the colon in healthy individuals. This viscoelastic mucus gel is protective against adhesion and invasion by microorganisms, bacterial toxins, and antigens. The mucus viscosity increases progressively toward the distal colon, separating bacteria selectively in the proximal colon and completely in the distal colon. Mucus in normal subjects is usually intact and devoid of bacteria, by contrast mucus barrier is broken and penetrated by bacteria and inflammatory cells in patients with colonic inflammation. The immune inclusion hypothesis postulates that the host mucosa maintains an adherent bacterial biofilm that develops immune tolerance with specific immune mechanisms. The bacterial biofilm, growing in the mucus matrix, would prevent contact of pathogenic bacteria with the intestinal mucosal wall. On the contrary, recent evidence indicates that bacteria are absent in mucus from healthy individuals and present in mucus from patients with inflammatory bowel disease. In inflammatory bowel disease alteration in the types of mucins or, alternatively, the altered mucus layer as a response to inflammation contributes to the underlying pathology by affecting the mucus barrier function.