Although the intestinal microbiota is largely beneficial, changes in bacterial populations or in the products of bacterial metabolism may contribute to diseases including cancer. The most known example is Helicobacter pylori, which, while establishing chronic infections in the stomach, is associated with an increased risk of gastric adenocarcinoma and mucosa associated lymphoid tissue (MALT) lymphoma. A broad range of proteins expressed by pathogenic bacteria can interact with host cells and directly manipulate the inflammatory reaction, which is closely related to the onset and progression of tumour. Moreover, their ability to promote anchorage-independent growth of cancer cells could facilitate thire metastatic potential.
Escherichia coli, one of the major inhabitants and normal flora of human intestine, could become highly pathogenic following the acquisition of genes coding for virulence factors such as necrotizing factor type 1 (CNF1). CNF1-producing E. coli are frequently detected in extraintestinal infections and soft tissue infections. It has been found that CNF1was over-represented in colon cancers, and colorectal cancer (CRC) was more frequently colonized by CNF1-producing E. coli than diverticulosis samples. The cytoplasmatic target of CNF1 is represented by the small G proteins of the Rho family, which are important switches to regulate many cellular processes such as actin cytoskeleton dynamics and organization. CNF1 stabilizes the G proteins in their GTP-bound active form enabling them to exert a permanent activity on their effectors, resulting a more malignant phenotype of cancer cells such as motility, invasiveness, metastasis, multinucleation, nuclear segmentation, amitotic division, multipolar mitosis and autophagy. It was reported that CNF1 inhibited apoptotic in epithelial cells through: (i) overexpressing anti-apoptotic members of the Bcl-2 family; (ii) protecting against the UVB-induced drop of the mitochondrial membrane potential and (iii) activating the pro-inflammatory Rac1/Akt/NF-kB pathway.
Taking into account all the above evidences, it is hypothesized that CNF1-producing E. coli act as passenger bacteria, reinforcing and favouring but not causing the development of colorectal cancer.