Tumorigenic bacteria in colorectal cancer: mechanisms and treatments

Abstract

Colorectal cancer (CRC) is the third most common and the second most fatal cancer. In recent years, more attention has been directedtoward the role of gut microbiota in the initiation and development of CRC. Some bacterial species, such as Fusobacterium nucleatum,Escherichia coli, Bacteroides fragilis, Enterococcus faecalis, and Salmonella sp. have been associated with CRC, based upon sequencingstudies in CRC patients and functional studies in cell culture and animal models. These bacteria can cause host DNA damage bygenotoxic substances, including colibactin secreted by pks + Escherichia coli, B. fragilis toxin (BFT) produced by Bacteroides fragilis,and typhoid toxin (TT) from Salmonella. These bacteria can also indirectly promote CRC by influencing host-signaling pathways,such as E-cadherin/β-catenin, TLR4/MYD88/NF-κB, and SMO/RAS/p38 MAPK. Moreover, some of these bacteria can contributeto CRC progression by helping tumor cells to evade the immune response by suppressing immune cell function, creating a proinflammatoryenvironment, or influencing the autophagy process. Treatments with the classical antibacterial drugs, metronidazole orerythromycin, the antibacterial active ingredients, M13@ Ag (electrostatically assembled from inorganic silver nanoparticles and theprotein capsid of bacteriophage M13), berberine, and zerumbone, were found to inhibit tumorigenic bacteria to different degrees. Inthis review, we described progress in elucidating the tumorigenic mechanisms of several CRC-associated bacteria, as well as progressin developing effective antibacterial therapies. Specific bacteria have been shown to be active in the oncogenesis and progression ofCRC, and some antibacterial compounds have shown therapeutic potential in bacteria-induced CRC. These bacteria may be usefulas biomarkers or therapeutic targets for CRC.