Microbiome & Chronic Diseases

Evidence Based Medicine

Colorectal cancer ⇒ Cancer {40000123}

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Colorectal cancer


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Gastroenterology, Oncology
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- The microbiomes of colorectal cancer subjects have increased abundance of a module for naphthalene degradation (M00534).
- The modules for cobalt/nickel transport systems (M00245 and M00246) are depleted in subjects with colorectal cancer.
- Enterotoxigenic Bacteroides fragilis (ETBF) secretes Bacteroides fragilis toxin (BFT), which decreases E-cadherin levels. This loosens the attachments between intestinal epithelial cells and results in exposure to many antigens. Moreover, decreased E-cadherin promotes intracellular migration of beta-catenin and accelerates carcinogenic-related signaling such as Wnt signaling. (1)

- Ren is a potential agent for colon cancer prevention.
- Administration of Ren effectively suppress DMH-induced colonic carcinogenesis. (4)

Shared Notes

  • [1.38
    - Fusobacterium nucleatum is enriched in human colonic adenomas relative to surrounding tissue, suggesting that it may play a role in early initiation of colorectal cancer.
    - Further supporting this idea, F. nucleatum colonization promoted and exacerbated tumorigenesis in the gut of APCmin/+ mice, although the mechanism of pathogenesis remains unknown.
  • [1.39
    - Chronic inflammation is an established risk factor for CRC, as patients with inflammatory bowel diseases (IBD) consistently have a higher risk than the general population of developing CRC.
    - An increase in pro-inflammatory species has been repeatedly reported in CRC patients.
    - The most prevalent and most described bacterium in CRC fecal and mucosa-associated microbiota is Fusobacterium nucleatum
  • [1.40
    - Odoribacter splanchnicus and Bacteroides sp. D20 were among the dominant strains in the guts of mutant mice.
    - Both strains induced strong protection against colitis and colorectal cancer when transferred to the gut of control mice.
    - O. splanchnicus in particular was sufficient to induce the development of intestinal immune cells and confer resistance against colitis and colorectal cancer, likely by inducing the development of specific intestinal immune cells.
  • [1.25
    - Fusobacterium nucleatum expresses adhesins, including FadA and Fap2, which bind to tumour cells and directly promote carcinogenesis by activating oncogenic Wnt/β-catenin signalling and dysregulating immune cell infiltration and antitumour immunity.
  • [1.41
    - Fusobacterium nucleatum subsp. vincentii, F. nucleatum subsp. animalis, Porphyromonas asaccharolytica, and Peptostreptococcus stomatis, all of which were found to be enriched in tumor and stool samples from CRC patients.
    - Patients with Peptostreptococcus bacteremia have an increased risk of developing , in particular Peptostreptococcus stomatis and Peptostreptococcus anaerobius. P. anaerobius has been found to be highly enriched in CRC patient stool and tissue.
    - Significant overabundance of P. gingivalis was found in fecal samples from CRC patients
    - Prevotella intermedia was associated with a higher risk of developing CRC and was identified in a multinational multicohort study of 526 metagenomic CRC fecal samples.
    - Overabundance of Parvimonas micra has been reported in CRC patient stool.
    Enterotoxigenic Bacteroides fragilis strains (ETBF) have been associated with CRC and is associated with sporadic CRC.
    - Tissues of patients with familial adenomatous polyposis (FAP) carry B. fragilis and Escherichia coli biofilms.
    -The genotoxin colibactin is produced by polyketide synthase-positive E. coli and induces DNA double-strand breaks in vitro and in vivo. It increases tumor formation in vitro alone, or in co-colonization with ETBF in FAP patients.
    - B. fragilis and some Prevotellaceae, but also F. nucleatum, produce succinate, an inducer of proinflammatory pathways via succinate receptor 1 on immune cells .
    - E. coli catabolism of lysine to succinate involves the intermediate l-2-hydroxyglutarate, an oncometabolite that is involved in epigenetic deregulation in certain cancers.
  • [1.8
    - Clostridiales species are significantly reduced in CRC patients compared with healthy controls.
    - Oral application of a mix of four Clostridiales strains (CC4) in mice prevented and even successfully treated CRC as stand-alone therapy. This effect depended on intratumoral infiltration and activation of CD8+ T cells.
    - Single application of Roseburia intestinalis or Anaerostipes caccae is even more effective than CC4.
    - The CC4 mix supplementation outperformed anti-PD-1 therapy in mouse models of CRC and melanoma.
  • [1.43
    - The direct bond of microbial proteins with E-cadherin of host epithelial cells can activate the β-catenin pathway, as expressed by Fusobacterium nucleatum, associated with colorectal cancer.
    - F. nucleatum, expressing Fap2 cell surface protein, inhibits immune cytotoxicity through interaction with T and NK cells
  • [1.44
    - Studies have demonstrated an enrichment of Fusobacterium nucleatum in human colorectal adenomas and carcinomas compared to adjacent normal tissue.
    - Experimental studies have shown that Fusobacterium nucleatum activates the WNT signaling pathway in colorectal carcinoma cells and may promote colorectal tumour growth
    - a higher amount of tissue Fusobacterium nucleatum DNA has been associated with advanced disease stage and a lower density of T-cells in human colorectal carcinoma tissue.

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