Microbe–Mucus Interface in the Pathogenesis of Colorectal Cancer

SIMPLE SUMMARY: The human gastrointestinal tract is colonized by a vast number of commensal microbes that are greatly beneficial, but at the same time pose a potential threat to the host. Direct contact of such microbes with intestinal epithelial cells can trigger unfavorable host responses that may, for example, contribute to tumor development. One mechanism of defense against such invaders is the transparent mucus layer that overlies the intestinal epithelium and forms a barrier to separate bacteria from the host. While functioning as a physical barrier, the mucus layer also shapes the composition of the microbial community by providing nutrients and attachment sites. In light of the pivotal role that intestinal microbes and a dysfunctional mucus layer have in gastrointestinal pathologies, including chronic inflammation and colorectal cancer, it is of great importance to understand the intricate mechanisms of microbe–mucus interactions in order to comprehend their contribution to disease pathogenesis and to identify new potential treatment strategies. ABSTRACT: Overlying gastrointestinal epithelial cells is the transparent mucus layer that separates the lumen from the host. The dynamic mucus layer serves to lubricate the mucosal surface, to protect underlying epithelial cells, and as a transport medium between luminal contents and epithelial cells. Furthermore, it provides a habitat for commensal bacteria and signals to the underlying immune system. Mucins are highly glycosylated proteins, and their glycocode is tissue-specific and closely linked to the resident microbiota. Aberrant mucin expression and glycosylation are linked to chronic inflammation and gastrointestinal cancers, including colorectal cancer (CRC). Aberrant mucus production compromises the mucus layer and allows bacteria to come into close contact with the intestinal epithelium, potentially triggering unfavorable host responses and the subsequent development of tumors. Here, we review our current understanding of the interaction between the intestinal microbiota and mucus in healthy and CRC subjects. Deep knowledge of the intricate mechanisms of microbe–mucus interactions may contribute to the development of novel treatment strategies for CRC, in which a dysfunctional mucus layer is observed.