Colorectal cancer: The epigenetic role of microbiome

Figure 1 The way gut microbiota induces CRC. Several factors affecting the normal behavior of microbiota such as low fiber and high-fat diets. This change might affect the number/types of gut bacteria or cause them to express different kinds of proteins and metabolites. A category of these metabolites could be oncogenic (oncometabolites) and trigger inflammation in gut epithelial cells leading to cancer initiation. Bacterial metabolites also could enhance cancer spreading and metastasis. CRC: Colorectal cancer.

Figure 2 Different pathways through which CRC develops. CRC: Colorectal cancer.

Figure 3 Different functions of butyrate in protecting against CRC. CRC: Colorectal cancer; HDAC: Histone deacetylase.

Figure 4 Different gut microbiota generate different oncometabolites. Bacteroides expresses specific signaling substances to activate toll-like receptor 2 (TLR 2), which functions in two different ways; activation of FOX3 to trigger Treg activation leading to inflammation. The other way is the activation of T helper 17 cells that also triggers inflammation. Flagellin, a product of flagellated bacteria, activates also TLR 5 to activate innate lymphoid cells 3 and then IL 17 and 22 that initiate inflammation. TLR 5 also works on nuclear factor κB to activate miR-21 that has a role in initiating cancer carcinogenesis (CRC). Meanwhile, Fusobacteria can stimulate a specific type of TLR that activates nuclear factor of activated T cell via calmodulin-based calcineurin to initiate CRC. CRC: Colorectal cancer; IL: Interleukin; ILC: lymphoid cells; NF-κB: Nuclear factor-κB; NFAT: Nuclear factor of activated T cell; TLR: Toll-like receptor; Treg: T regulatory cell.