The gut microbiota can orchestrate the signaling pathways in colorectal cancer

Abstract

Current evidence suggests that bacteria contribute to the development of certain cancers, such as colorectal cancer (CRC), partly by stimulating chronic inflammation. However, little is known about the bacterial impact on molecular pathways in CRC. Recent studies have demonstrated how specific bacteria can influence the major CRC‐related pathways, i.e., Wnt, PI3K‐Akt, MAPK, TGF‐β, EGFR, mTOR, and p53. In order to advance the current understanding and facilitate the choice of pathways to investigate, we have systematically collected and summarized the current knowledge within bacterial altered major pathways in CRC. Several pro‐tumorigenic and anti‐tumorigenic bacterial species and their respective metabolites interfere with the major signaling pathways addressed in this review. Not surprisingly, some of these studies investigated known CRC drivers, such as Escherichia coli, Fusobacterium nucleatum, and Bacteroides fragilis. Interestingly, some metabolites produced by bacterial species typically considered pathogenic, e.g., Vibrio cholera, displayed anti‐tumorigenic activities, emphasizing the caution needed when classifying healthy and unhealthy microorganisms. The results collectively emphasize the complexity of the relationship between the microbiota and the tumorigenesis of CRC, and future studies should verify these findings in more realistic models, such as organoids, which constitute a promising platform. Moreover, future trials should investigate the clinical potential of preventive modulation of the gut microbiota regarding CRC development.

Inhibition of the Occurrence and Development of Inflammation-Related Colorectal Cancer by Fucoidan Extracted from Sargassum fusiforme

“…As the intestine is the most dominant organ inhabited by human flora, the development of several enteropathies is inextricably linked to microorganisms . There is growing evidence that a dysbiosis of the intestinal microflora can trigger and promote diseases mediated by chronic inflammation, including CRC. − Bacteroides fragilis and Fusobacterium nucleatum are the key bacteria responsible for colorectal carcinogenesis . In patients with CRC, the ratio of Firmicutes/Bacteroidetes in the stool is significantly higher than that of controls .…”

Intake of Pro‐ and/or Prebiotics as a Promising Approach for Prevention and Treatment of Colorectal Cancer

“…These proteins activate the intestinal immune system via downstream signaling upon recognition of microbial antigens, [ 51 ] and examples of those implicated in colitis‐associated carcinogenesis, include Toll‐like receptors (TLRs), nucleotide‐binding oligomerization‐like receptors, and absent in melanoma 2‐like receptors. [ 81 ] Researchers have discovered that Lactobacillus acidophilus, Bifidobacteria bifidum , and Bifidobacteria infantum are effective at enhancing expression of TLR2 and reducing expression of TLR4 and COX‐2 to curb inflammation. [ 82 ] As well, Lentinus edodes polysaccharides appears to be capable of binding TLR4 to reduce secretion of VEGF‐C by cancer‐associated fibroblasts and inhibiting lymphangiogenesis and lymphatic metastasis in CRC.…”

New Insights into the Relationship between Gut Microbiota and Radiotherapy for Cancer

“…Gut microbiota can promote the development of certain cancers, such as CRC, by stimulating chronic inflammation [ 29 ]. At present, the active role of the “inflammasome-microbiome axis” in the occurrence and progression of CRC has been confirmed [ 25 ].…”

“…had pathogenicity that affected the TGF-β signaling pathway. In addition, E. coli and its related toxins were found to be naturally associated with the p53 and Wnt signaling pathways [ 29 , 34 ]. Other studies have demonstrated the role of Helicobacter pylori in accelerating the development of gastric cancer, while the Yes-associated protein 1, a key effector of the Hippo pathway, is also involved in this process [ 35 ].…”