## 7 Colorectal Cancer
### Microbiota in Colorectal Cancer  
The main mechanism by which the gut microbiota can influence CRC development is the release of inflammatory agents, which promote the change of normal cells to cancerous mutants [135]. [PERSON] et al. reported that the Firmicutes Cluster 1, being important SCFA producers, as well as the Bacteroidetes Cluster 1, were significantly less abundant in CRC biopsy microbiota than healthy controls; in addition, Firmicutes and Bacteroidetes phyla as well as _Prevotella_ genera were more abundant [136]. Other studies have found _Roseburia_, _Ruminococcus_, _Oscillilbacter_, _Fusobacterium_ (especially _F. nucleartum_ and _F.arium_), and _Porphyromonas_ to be more abundant in the faecal samples of CRC patients then controls, as well as Bacteroides and _Prevotella_ (_P. stercorea_). [PERSON] et al. reported that the microbiota of CRC patients was significantly less diverse than that of healthy subjects (alpha diversity analysed by richness, phylogenetic diversity, Shannon diversity, and Simpson diversity), and that CRC patient microbiota was richer in members of _Clostridium XIVa_, _Fusobacterium_, _Parcimonas_, and _Peptostreptococcus_ genera. They also note that the presence of _Fusobacterium_ bacteria was significantly associated with lymphatic invasion of cancer cells (\(p<0.05\)) [136]. In addition, [PERSON] et al. reported that the cancer microbiota varies depending on the placement of the CRC. _Alistipes_, _Akkermansia_, _Halomonas_, and _Shewanella_ numbers were significantly higher in individuals with rectal and distal cancers, while _Faecalibacterium_, _Blautia_, and _Clostidium_ were more abundant in individuals with proximal cancer [136] (Table 7). CRC patients' microbiota undergoes specific rearrangement. Abundance of Firmicutes and Bacteroidetes, reported as the commensal gut microbiota, is significantly decreased, while species that are not common or rare in gut microbiota are increasing. Faecal and mucosal samples from 42 CRC cases and 89 matched controls. 16S sequencing [136]; faecal and mucosal samples from 59 patients undergoing surgery for CRC, 21 individuals with polyps, and 56 healthy controls. 16S rRNA amplicon sequencing, qPCR. Metabolomics analyses, that is, high-performance liquid phase chromatography and gas chromatography coupled with tandem mass spectrometry [137]; faecal samples from 203 colorectal cancer and 236 healthy subjects. Probe-based duplex quantitative PCR (qPCR) assays [138]; faecal samples from 10 CRC patients and 11 healthy controls. 16S rRNA amplicon sequencing [139]. Several studies have reported that certain bacteria appear to be directly associated with the pathogenesis of colorectal cancer, and bacterial species such as _Enterococcus faecalis, Bacteroides fragilis, Streptococcus bovis, Helicobacter pylori, Fusobacterium_ spp., and _Escherichia_ coli have been reported to significantly influence the development of CRC [135; 136]. [PERSON] et al. note that _Bacteroides fragilis_ is able to induce colitis and colonic tumors in an _ApCMin/+_ mice model by activating a lymphocytes T helper type 17 (Th17) inflammatory response [54]. Significant enrichment in _Fusobacterium_ spp. has already been reported in samples from colorectal patients in multiple studies [138; 139]. Moreover, studies show that the oral pathogen _F. nucleatum_ adheres to colonic epithelial cells through its FadA (_Fusobacterium nucleatum_ adhesion protein) adhesion protein. FadA activates \(\beta\)-catenin signaling by binding to E-cadherin in colonic cells, which deregulates inflammatory and oncogenic responses [135; 140]. Several researchers have also shown that a high-abundance of _F. nucleatum_ induces a series of specific tumour molecular events, including CpG island methylator phenotype; microsatellite instability; and genetic mutations in _braf, chd7, chd8_, and _tp53_[140]. _Enterococcus faecalis_, repeatedly found in CRC patients, produces reactive oxygen and nitrogen species that directly lead to DNA breaks, point mutation, and chromosomal instability [73]. Even though _H.