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 directed toward 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 sequencing studies in CRC patients and functional studies in cell culture and animal models. These bacteria can cause host DNA damage by genotoxic 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 contribute to CRC progression by helping tumor cells to evade the immune response by suppressing immune cell function, creating a proinflammatory environment, or influencing the autophagy process. Treatments with the classical antibacterial drugs, metronidazole or erythromycin, the antibacterial active ingredients, M13@ Ag (electrostatically assembled from inorganic silver nanoparticles and the protein capsid of bacteriophage M13), berberine, and zerumbone, were found to inhibit tumorigenic bacteria to different degrees. In this review, we described progress in elucidating the tumorigenic mechanisms of several CRC-associated bacteria, as well as progress in developing effective antibacterial therapies. Specific bacteria have been shown to be active in the oncogenesis and progression of CRC, and some antibacterial compounds have shown therapeutic potential in bacteria-induced CRC. These bacteria may be useful as biomarkers or therapeutic targets for CRC.

Alterations of the Gut Microbiome and Fecal Metabolome in Colorectal Cancer: Implication of Intestinal Metabolism for Tumorigenesis

“…Ruminococcus bicirculans , a new Firmicutes species belonging to the dominant human colonic microbiota ( Wegmann et al, 2014 ), was negatively correlated with arachidonic acid and tryptophan. In addition, we focused on Bacteroides fragilis because it promotes CRC progression via multiple mechanisms, such as weakening adherence junctions, breakdown of the extracellular matrix, and reorganization of the cytoskeleton ( Li et al, 2021 ). Enterotoxigenic Bacteroides fragilis (ETBF) produces Bacteroides fragilis toxin, which has been associated with acute diarrheal disease, inflammatory bowel disease, and colorectal cancer (CRC) ( Henstra et al, 2021 ).…”

Inhibition of the Occurrence and Development of Inflammation-Related Colorectal Cancer by Fucoidan Extracted from Sargassum fusiforme

“…15−17 Bacteroides fragilis and Fusobacterium nucleatum are the key bacteria responsible for colorectal carcinogenesis. 18 In patients with CRC, the ratio of Firmicutes/Bacteroidetes in the stool is significantly higher than that of controls. 19 In addition, the bacterial metabolites, including short-chain fatty acids, are essential for protecting the gut mucosal barrier and inhibiting intestinal inflammation.…”

“…As the intestine is the most dominant organ inhabited by human flora, the development of several enteropathies is inextricably linked to microorganisms . There is growing evidence that a dysbiosis of the intestinal microflora can trigger and promote diseases mediated by chronic inflammation, including CRC. − Bacteroides fragilis and Fusobacterium nucleatum are the key bacteria responsible for colorectal carcinogenesis . In patients with CRC, the ratio of Firmicutes/Bacteroidetes in the stool is significantly higher than that of controls .…”

Multi-Omics Integration Reveals the Crucial Role of Fusobacterium in the Inflammatory Immune Microenvironment in Head and Neck Squamous Cell Carcinoma

“…Dysbacteriosis is reported to be involved in tumor carcinogenesis and progression through various mechanisms, including mutagenesis and epigenetic and immune activity changes of the host ( 4 , 5 ). Bacteroides fragilis produces genotoxin B. fragilis toxin (BFT) and causes the host DNA damage to initiate colorectal carcinogenesis ( 6 ); Fusobacterium nucleatum targets innate immune signaling and miRNA-mediated autophagy to result in chemoresistance of colorectal cancer ( 7 ). In addition, the bacterial metabolite butyrate has been identified as a histone deacetylation inhibitor, suggesting that bacteria may influence tumor progression by affecting chromatin accessibility ( 8 ).…”