## 4 Discussion
### Metabolic Pathways of Top Scoring Enzymes
These enzymes contribute to key biochemical processes regulating energy metabolism and detoxification. Butyrate is an essential mediator between the gut microbiota and host metabolic health. Therefore, it has regulatory effects on metabolic functions such as body weight, body composition, and glucose homeostasis, absorbing and metabolizing though tissues and cells beyond the colon [89]. The microorganisms That Synthesize the Enzymes Identified by the EC-Nomenclature-Based G-S-M and Their Association with CRC Development  
The microbial community of the gut has a crucial role in safeguarding the host from harmful microorganisms. Also, the microbial community influences the immune system and regulates metabolic processes, therefore, it is recognized as an endocrine organ. This dynamic interplay between the host and the microbiome is pivotal in human physiology and metabolism, encompassing functions such as synthesizing essential vitamins like vitamin K, extracting energy from indigestible carbohydrates like pectin, modulating the human immune system, and preventing colonization by enteropathogenic bacteria [7; 90; 91; 92]. The system's homeostasis and the abundance of microbiota in the gut are regulated by factors such as the optimal pH range, suitable oxygen concentration, and abundant nutrients. Disruptions within the typical composition of the intestinal microbiome pose significant challenges [93; 94; 95]. Dysbiosis, characterized by an imbalance in the symbiotic relationship between the host and the intestinal microbiota, has been identified as a potential factor contributing to several diseases, such as inflammatory bowel disease (IBD) [96], hepatocellular carcinoma (HCC) [97], and colorectal cancer (CRC) [98; 99]. The onset of these diseases is often noticed by disruptions in the normal microbiota, prompting immune system activation and subsequent inflammation [100]. Given the increased susceptibility to CRC in individuals with IBD, and the observed dysbiosis in some cases, it is reasonable to infer that CRC associated with IBD is preceded by a phase of dysbiosis. Consequently, the microbiome is increasingly implicated as a significant factor in the onset and/or progression of colonic carcinogenesis [99; 101; 102]. The gut microbiome can be related to disease formation and prognosis, and hence it is important to understand the underlying mechanisms involved. It is important to note that, while some bacteria are known to cause infections in humans, others are part of the normal microbiota. The pathogenicity of these bacteria can vary, and their impact on human health depends on various factors, including the specific strain and the host's immune system. The enzymes within the top three significant enzyme groups (glycosidases (EC: 3.2.10), hydro-lyases (EC: 4.2.1), and CoA-transferases (2.8.3)) identified by the EC-nomenclature-based G-S-M on the CRC-associated metagenomic dataset are synthesized by different organisms. As shown in Figure 13, _Eschericia coli_ (_E. coli_), Salmonella enterica, Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pneumoniae, and Clostrtidoides dificle can be relevant for CRC development. Additionally, as shown in Figure 14, _E. coli_, _Salmonella enterica_, _Klebsiella pneumoniae_, and _Citrobacter koseri_ were highlighted by the XGB and SKB feature selection methods coupled with the RF classifier. E. coli is reported in the literature to have a higher abundance in CRC patients compared with controls [103]. Recent studies have strengthened the association between certain strains of E. coli and CRC. Notably, specific E. coli strains and Klebsiella pneumoniae produce coliactin, a genotoxic that can damage DNA, potentially leading to cancer development [104]. The research indicates that these colibactin-producing E. coli strains are more prevalent in industrialized countries, correlating with higher CRC incidence rates. This suggests that targeting these bacterial strains through vaccines or other treatments could be a viable strategy to reduce cancer risk.