Role of the Gut Microbiota and Its Metabolites in Tumorigenesis or Development of Colorectal Cancer

Abstract

Colorectal cancer (CRC) is the most common cancer of the digestive system with high mortality and morbidity rates. Gut microbiota is found in the intestines, especially the colorectum, and has structured crosstalk interactions with the host that affect several physiological processes. The gut microbiota include CRC‐promoting bacterial species, such as Fusobacterium nucleatum, Escherichia coli, and Bacteroides fragilis, and CRC‐protecting bacterial species, such as Clostridium butyricum, Streptococcus thermophilus, and Lacticaseibacillus paracasei, which along with other microorganisms, such as viruses and fungi, play critical roles in the development of CRC. Different bacterial features are identified in patients with early‐onset CRC, combined with different patterns between fecal and intratumoral microbiota. The gut microbiota may be beneficial in the diagnosis and treatment of CRC; some bacteria may serve as biomarkers while others as regulators of chemotherapy and immunotherapy. Furthermore, metabolites produced by the gut microbiota play essential roles in the crosstalk with CRC cells. Harmful metabolites include some primary bile acids and short‐chain fatty acids, whereas others, including ursodeoxycholic acid and butyrate, are beneficial and impede tumor development and progression. This review focuses on the gut microbiota and its metabolites, and their potential roles in the development, diagnosis, and treatment of CRC.

Antitumor Effect and Gut Microbiota Modulation by Quercetin, Luteolin, and Xanthohumol in a Rat Model for Colorectal Cancer Prevention

“…These incongruent trends can be explained since it has been observed that the association of Christensenellaceae with CRC depends on the type of specific mutation present [ 66 , 67 ]. On the other hand, as shown in Table 3 , we observed a significant decrease in the abundance of the family Enterobacteriaceae in the luteolin cohort, which may be related to an unhealthy state (due to the presence of lipopolysaccharide in this family, as well as other virulence factors), since this family is associated with CRC due to the production of the organic compound trimethylamine n-oxide [ 68 ]. Other families, such as Eggerthellaceae and Anaerovoracaceae, showed a reduction in the luteolin cohort, while the Clostridia vadinBB60 group and Butyricicoccaceae experienced an increase.…”

Relationship between Helicobacter pylori infection and colorectal polyp/colorectal cancer

“…The quantity of intestinal flora varies with the origin and evolution of CRC[ 67 ]. Simultaneously, increased abundance of pro-tumor bacteria such as polyketide synthase-positive (pks+) Escherichia coli ( E. coli ), enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum can promote intestinal inflammation via toxins or metabolites, facilitate tumor cell proliferation and migration, and create an immunosuppressive microenvironment that limits anti-tumor immunity[ 68 , 69 ]. The preceding data indicate that the intestinal flora plays an important role in the development of CRC and influences tumor chemotherapy and immunotherapy[ 70 ].…”

Inhibitory Effects of Soluble Dietary Fiber from Foxtail Millet on Colorectal Cancer by the Restoration of Gut Microbiota

“…The gut microbiota communicates with the host immune system through pattern recognition receptor signaling, inflammasome, and cytokines. 17 As a natural functional component, dietary fiber is usually divided into two categories: insoluble dietary fiber (IDF) and soluble dietary fiber (SDF); among them, SDF has significant antitumor activity and can have a prebiotic effect by increasing beneficial bacteria and improving intestinal environment. 18 Zhu et al found that sweet potato pomace SDF can be thoroughly decomposed by microorganisms distributed in the human digestive tract, regulating the structure of the human intestinal bacterial community, which has a significant effect on prevention and treatment of colon cancer and other diseases.…”

“…Accumulating studies have found that some specific bacteria, such as Fusobacterium nuclei, Escherichia coli, and Bacteroides fragilis, are associated with multiple occurrence mechanisms of colorectal cancer. The gut microbiota communicates with the host immune system through pattern recognition receptor signaling, inflammasome, and cytokines . As a natural functional component, dietary fiber is usually divided into two categories: insoluble dietary fiber (IDF) and soluble dietary fiber (SDF); among them, SDF has significant antitumor activity and can have a prebiotic effect by increasing beneficial bacteria and improving intestinal environment .…”