Colon mucus in colorectal neoplasia and beyond

Abstract

Little was known about mammalian colon mucus (CM) until the beginning of the 21^st century. Since that time considerable progress has been made in basic research addressing CM structure and functions. Human CM is formed by two distinct layers composed of gel-forming glycosylated mucins that are permanently secreted by goblet cells of the colonic epithelium. The inner layer is dense and impenetrable for bacteria, whereas the loose outer layer provides a habitat for abundant commensal microbiota. Mucus barrier integrity is essential for preventing bacterial contact with the mucosal epithelium and maintaining homeostasis in the gut, but it can be impaired by a variety of factors, including CM-damaging switch of commensal bacteria to mucin glycan consumption due to dietary fiber deficiency. It is proven that impairments in CM structure and function can lead to colonic barrier deterioration that opens direct bacterial access to the epithelium. Bacteria-induced damage dysregulates epithelial proliferation and causes mucosal inflammatory responses that may expand to the loosened CM and eventually result in severe disorders, including colitis and neoplastic growth. Recently described formation of bacterial biofilms within the inner CM layer was shown to be associated with both inflammation and cancer. Although obvious gaps in our knowledge of human CM remain, its importance for the pathogenesis of major colorectal diseases, comprising inflammatory bowel disease and colorectal cancer, is already recognized. Continuing progress in CM exploration is likely to result in the development of a range of new useful clinical applications addressing colorectal disease diagnosis, prevention and therapy.

Keywords: Colon, Colon mucus, Mucins, Goblet cells, Gut microbiota, Inflammatory bowel disease, Colorectal cancer

Core Tip: Until recently colon mucus (CM) importance was largely ignored because its structure and functions were obscure. It is now known that human CM comprises a dense inner layer impenetrable for bacteria and a loose outer layer providing a habitat for abundant commensal microbiota. Mucus barrier integrity is essential for maintaining homeostatic balance between colonic mucosa and gut microbiota, and its impairment opens direct bacterial access to the epithelium, which induces inflammation and can cause severe disorders, including inflammatory bowel disease and colorectal cancer. Recent advances in colorectal mucus exploration and emerging new clinical applications based on this knowledge are discussed.