Fusobacterium and Colorectal Cancer

Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide and its pathogenesis has been extensively explored over the past decades. Recently, microorganisms in the gastrointestinal tract have emerged as potential etiological agents. In particular, a direct proportional association between Fusobacterium and CRC has been described. Since then, the functional impact of Fusobacterium in CRC development has been studied using various mouse models. Although some epidemiologic studies did not establish an obvious relationship between Fusobacterium and CRC, numerous pathogenic mechanisms leading to the disease have been described. For instance, Fusobacterium can activate the E-cadherin/β-catenin signaling pathway and is associated with particular epigenetic phenotype, such as microsatellite instability (MSI) and hypermethylation, via its strong adhesive and invasive abilities resulting in malignant transformation of epithelial cells. Also, Fusobacterium could alter the tumor microenvironment (TME) significantly by myeloid-derived suppressor cells (MDSCs), tumor associated macrophages (TAMs), and tumor associated neutrophils (TANs) recruitment and local immune suppression. Herein, we provide an in-depth review of the relationship between Fusobacterium and colorectal cancer. In light of the emergence of microbiome-based therapeutics, potential therapies and preventive strategies for colorectal cancer related to Fusobacterium are also discussed.

Therapeutic Targeting of the Colorectal Tumor Stroma

“…This mechanism is prevalent in MSI tumor cells, which often lose membrane HLA molecules, [81][82][83] so they escape T-cell cytotoxicity but not NK cell cytotoxicity. This reduces their metastatic potential 52 Fusobacterium nucleatum, which are associated with lower densities of T cells 90 , lymph node metastasis 89 , and poor outcomes, 91 require further study 92 .…”

Antimicrobial activity and toxicity profile of selected southern African medicinal plants against neglected gut pathogens

“…11 Other pathogens that are isolated in intra-abdominal infections include Helicobacter pylori as well as Fusobacterium species. 3,5,12 Helicobacter pylori infects more than 50% of the world's population; however, only a small percentage of patients develop severe disorders. 13 People that are most likely to be infected are from developing countries.…”

“…These species are associated with severe infections and are often related to colorectal cancer, which is the third most common cancer worldwide. 12,15 A wide range of antibiotics and treatment regimens are used for the treatment of intra-abdominal infections. Increased antibiotic resistance is the main cause of treatment failure.…”

Metabolic models predict bacterial passengers in colorectal cancer

“…On the other hand, Fusobacterium is also hypothesized to drive tumorigenesis via its unique adhesion protein (FadA) binding to E-cadherin and activating betacatenin signaling which in turn regulates inflammatory and potentially oncogenic responses. In our current analysis, F. nucleatum are among the bacteria that most strongly benefit from the CRC metabolites and may thus be regarded as "driving passengers" [77]. Apart from a few described examples, further research is needed to chart the mechanisms allowing the different constituents of the human microbiome to promote tumor initiation and progression.…”