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Disease ⇒ Colorectal cancer ⇒ Cancer {40000123}

Record Keys


Type:
Disease
Definition:
Colorectal cancer
Parent:

Details


Initialisation date:
2019-05-15
Other Terms:
CRC

Links


Meta Information


MedDra ID:
10061451
MedDra Level:
pt
ICD:[  ]
Category:
Gastroenterology, Oncology
Zone:[  ]
Mechanism:[  ]

Notes:


- 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)

- bacteria like #Acidaminobacter, #Phascolarctobacterium and #Citrobacter were present in significant number in colorectal cancer (CRC) patient’s stool samples.

References Notes


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Shared Reference Notes


  • [1.49
    - 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.
  • [1.50
    - 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
  • [1.51
    - #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.
  • [1.29
    - #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.
  • [1.52
    - 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.
  • [1.53] [#Antibiotic Therapy
  • [1.9
    - #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.
  • [1.54
    - 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
  • [1.55
    - CRC mouse model > Oral microbiota alterations change > the gut bacterial composition within tumors but not in adjacent peritumor tissues. - Buccal #Fusobacterium nucleatum migrates > to the CRC locus > impairs the therapeutic efficacy and prognosis of #Radiotherapy. Administration of a specific antibiotic, metronidazole > abrogates the adverse effects of oral microbiome fluctuation on #Radiotherapy for CRC.
  • [1.32
    - #Helicobacter hepaticus (Hhep) colonization reduces colorectal cancer burden in mice. - Hhep induces CD4+ Tfh cell- and B cell-dependent anti-colorectal cancer immunity
  • [1.57] [#Iron (ferric)
    - #Bifidobacteriaceae > binding Fe in the large intestine > limiting the formation of free radicals associated with Fe >reducing the risk of colorectal cancer
  • [1.47] [#Alzheimer’s disease
    - Serum #TMAO levels in AD/CRC patients are higher than those in healthy people, and its concentrations may be positively correlated with AD/cancer progression
  • [#Hydrogen sulfide] - H2S at a safe and nontoxic concentration can protect not only healthy cells, such as neurons, but also cancerous cells from apoptosis. - In a variety of cancers, including ovarian #Cancer, oral #Cancer, thyroid #Cancer, colon #Cancer, #Breast cancer, etc., the upregulation of H2S-producing enzyme CBS > can enhance the proliferation ability of #Cancer cells and make #Cancer cells more sensitive to it
  • - #Vitamin D supplementation could regulate the steady state of intestinal flora in colorectal cancer (CRC) mice and regulate the integrity of the #Akkermansia muciniphila-mediated intestinal barrier, thereby playing a role in the reversal of CRC.
  • [#Short Chain Fatty Acid] - SCFAs > maintaining the integrity of the intestinal barrier to reduce the risk of colon cancer
  • [1.58] [#Crohn’s disease, #Inflamatory bowel disease] [#Common consumer products
    - #Triclosan (TCS), an antimicrobial agent found in thousands of consumer products > exacerbates #Colitis and #Colitis-associated colorectal tumorigenesis in animal models. - intestinal commensal microbes > microbial β-glucuronidase (GUS) enzymes > mediate metabolic activation of #Triclosan in the colon > gut toxicology.
  • [1.25
    - #Enterococcus faecalis levels associated with variants in the MED13L locus, which has been linked to colorectal cancer.
  • [1.59] [#Antibiotic Therapy
  • [1.45
    - Increases in #Enterococcus faecalis and #Escherichia coli enhance the production of intestinal inflammatory signaling molecules, IFN-γ and IL-4. In both IBD and CRC, #Fusobacterium nucleatum elicits strong pro-inflammatory responses
  • [#Tryptophan] - Around 5% of Trp > metabolized by gut bacteria into #Indole and indolic compounds > can bind to pregnane X receptors (PXR) and aryl hydrocarbon receptor (AhR) > promote intestinal homeostasis, enhance barrier function and tight junctions, reduce permeability, regulate intestinal immune tolerance. - Alteration in Trp metabolism begin at early stages of CRC and allow immune evasion umor microenvironment (i.e. the oncogene c-MYC cab accelerate Trp uptake) with an increase in IDO1 and T cell inactivation. - Reduction in indoles production is observed in CRC and the administration of microbial indolic metabolites, diindolylmethane or I3C (AhR ligands), reduces tumor formation
  • [#Serotonin (5-hydroxytryptamine)] - #Tryptophan > serotonin > can exhibit both a protective and detrimental role. For example, activation of serotonin receptors, 5-HTR1B and 5-HTR2B stimulate tumor angiogenesis and cell proliferation. SCFAs can induce the production and release of serotonin though. In normal conditions, serotonin seems to have mainly a protective role but dysregulation of its production is linked to cancer promotion.
  • [1.28] [#Bile Acids
    - Butyrate producing bacteria such as #Eubacterium spp. are capable of transforming primary BAs to secondary BAs such as: #Lithocholic acid and #Deoxycholic acid, which are potentially cytotoxic and have been linked to colorectal cancer and cholesterol GS formation.
  • [1.36] [#Parvimonas micra
    - four species of two genera are found to be associated with CRC: #Parvimonas micra, #Parvimonas sp., #Peptostreptococcus stomatis, and #Peptostreptococcus anaerobius.
  • [1.60] [#Western-style diet
    - higher levels of #Polyketide synthase (pks+) #Escherichia coli in tumors of those who relied on Western-style diets.
  • [1.44
    - #Butyrate treatment of epithelial cells boosted IL-18 production via a GPR109a-mediated pathway, promoting stomach homeostasis and defending against colorectal carcinogenesis
  • [1.61
    - Betabaculus virus, Epsilon15likevirus, Mulikevirus, and Punalikevirus were particularly enriched in CRC patients and associated with increased severity and mortality. - Viral infections such as human papillomaviruses (HPV), human polyomaviruses,human herpesviruses,human bocavirus, and Inoue–Melnick virus were found in cancer tissues compared with adjacent normal tissues of CRC patients.
  • - Malasseziomycetes and decreased Saccharomycetes were observed in CRC patients. The distribution of fungal genera #Aspergillus, #Malassezia, #Rhodotorula, Pseudogymnoascus, Kwoniella, Talaromyces, Debaryomyces, Moniliophthora, Pneumocystis, and Nosemia was altered in CRC.
  • [1.62
    -The #Sulfur microbial diet, was characterized by high intakes of low-calorie beverages, french fries, red meats, and processed meats and low intakes of fruits, yellow vegetables, whole grains, legumes, leafy vegetables, and cruciferous vegetables. - Adherence to the #Sulfur microbial diet was associated with an increased risk of CRC, suggesting a potential mediating role of sulfur-metabolizing bacteria in the associaton between diet and CRC.
  • [1.46] [#Human end-stage renal disease
    - #TMAO is a major risk factor for cardiovascular disease, renal fibrosis and functional impairment, #Atherosclerosis, and colorectal cancer.
  • [#Hepatocellular cancer] [#Secondary bile acids] - excessive production of the secondary BA deoxycholic acid triggers the expression of inflammatory and tumorigenic factors in hepatic stellate cells (HSCs), contributing to hepatocellular carcinoma development. Secondary BAs might also activate farnesoid X receptor (FXR) and elevate the risk of developing colorectal cancer and hepatocellular carcinoma.
  • [1.63
    - Luminal microbiota are more strongly implicated in metabolic exchange with the host, while mucosa-associated microbiota can directly contact and affect IECs. - mucosa-associated microbiome in tumors differs from that of non-neoplastic areas within the same individuals. - localization of CRC (proximal vs. distal) may also influence microbiome composition
  • [1.2
    - bacteria like #Acidaminobacter, #Phascolarctobacterium and #Citrobacter were present in significant number in colorectal cancer (CRC) patient’s stool samples.
  • - #Butyrate, on the other hand, induces apoptosis in malignant epithelial cells that line the large intestine, lowering the risk of bowel cancer while also providing energy to gut cells.
  • - Genera which produce #Butyrate were almost absent in colorectal cancer patient’s stool.
  • [1.19
    - in colon cancers #Candida > predictive of metastatic disease and attenuated cellular adhesions. - #Candida DNA is enriched in tumors and predictive of reduced survival in GI cancers
  • [1.64
    - #Ascomycota and #Basidiomycota phyla dominated the intratumor mycobiome. The #Ascomycota to #Basidiomycota ratio (A/B ratio) was highest in colon cancer, due to abundant #Saccharomycetes, and lowest in #Melanoma, due to abundant #Malasseziomycetes.
  • [1.33] [#Inflamatory bowel disease
    - Morganella morganii is enriched in the gut microbiota of both IBD and CRC patients. - Morganella morganii-derived small-molecule genotoxins—termed the #Indolimines—that elicited DNA damage in cell-based and cell-free assays. - In a mouse model of colon cancer, M. morganii exacerbated tumor burden, but a mutant form of the bacteria unable to produce indolimine did not.
  • [1.65
    - 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.

Common References