Microbiome & Chronic Diseases

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Disease ⇒ Cancer ⇒ Colorectal cancer {40000123}

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Colorectal cancer


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Gastroenterology, Oncology
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- The elevated abundance of certain bacterial species such as Fusobacterium nucleatum and Parvimonas micra in CRC patients is often associated with the development of the disease
- 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.

Shared Reference Notes

  • [1.1
    - 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.
  • [1.2
    - 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
  • [1.3
    - #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.
  • [1.4
    - #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.
  • [1.5
    - 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.
  • [1.6] [#Antibiotic Therapy
  • [1.7
    - #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.
  • [1.8
    - 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
  • [1.9
    - 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.
  • [1.11
    - #Helicobacter hepaticus (Hhep) colonization reduces colorectal cancer burden in mice. - Hhep induces CD4+ Tfh cell- and B cell-dependent anti-colorectal cancer immunity
  • [1.12] [#Iron (ferric)
    - #Bifidobacteriaceae > binding Fe in the large intestine > limiting the formation of free radicals associated with Fe >reducing the risk of colorectal cancer
  • [1.13] [#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
  • [1.14] [#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.
  • [1.15
    - #Enterococcus faecalis levels associated with variants in the MED13L locus, which has been linked to colorectal cancer.
  • [1.16] [#Antibiotic Therapy
  • [1.17
    - 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
  • - #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.
  • [1.18] [#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.
  • [1.19] [#Parvimonas micra
    - four species of two genera are found to be associated with CRC: #Parvimonas micra, #Parvimonas sp., #Peptostreptococcus stomatis, and #Peptostreptococcus anaerobius.
  • [#Western-style diet] - higher levels of #Polyketide synthase (pks+) #Escherichia coli in tumors of those who relied on Western-style diets.
  • [1.21
    - #Butyrate treatment of epithelial cells boosted IL-18 production via a GPR109a-mediated pathway, promoting stomach homeostasis and defending against colorectal carcinogenesis
  • [1.22
    - 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.
  • [1.23
    -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.
  • [1.24] [#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.
  • [1.25
    - 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
  • [1.26
    - 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.
  • [1.27
    - 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
  • [1.28
    - #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.
  • [1.29] [#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.
  • [#Sport] - #Physical activity is associated with reduced risks of colorectal cancer (CRC) incidence, recurrence and mortality. - exercise can modify the gut microbiota, and these changes are inverse to the changes seen with CRC. - exercise mediating changes promote the antitumorigenic characteristics of the gut microbiota.
  • [1.31] [#Crohn’s disease] [#Bacteriophage, #Western-style diet
    - the abundance of a class of crAss-like phages, a group of related viruses that includes some of the most abundant viruses of the human gut, were higher in populations with non-westernized dietary habits - several types of crAss-like phages were present at decreased levels in people with #Rheumatoid Arthritis, #Systemic lupus erythematosus, #Ulcerative Colitis and Crohn disease, and at increased levels in people with colon cancer.
  • [1.32
    - #Ammonia accumulates in tumors and reduces T cell function in vitro and in vivo. - #Ammonia decreases T cell transsulfuration leading to altered redox status. - Clearance of #Ammonia reactivates T cells and decreases colorectal cancer.
  • [1.33
    - 73.0% increase in CRC risk among #Appendectomy cases throughout 20 years follow-up
  • [1.34] [#Pancreatic Cancer] [#Bacteroides fragilis toxin
    - Enterotoxigenic #Bacteroides fragilis (ETBF) produces #Bacteroides fragilis toxin (BFT), which is associated with acute diarrheal, inflammatory bowel disease, and colorectal cancer (CRC).
  • [1.35
    - Polyamines can feed #Cancer cells for growth and any polyamines, regardless of their sources (i.e., dietary, microbial, and tissues) can drive tumorigenesis. - Tumor cells require more polyamines for growth than healthy cells - #Cancer patients have increased #Polyamine levels in the blood and urine. - #Polyamine concentrations appear to be increased in CRC tissues compared to healthy tissues.
  • [#Colon adenomas] [#Deoxycholic acid, #Secondary bile acids, #Ursodeoxycholic acid] - UDCA has microbiome-changing and DCA‐lowering prpperties. - treatment with UDCA, decreased recurrence of adenomas with high-grade dysplasia. - DCA also stimulates the uptake of polyamines in CRC cells, which also have tumorigenic effects.
  • - CRC patients had lower stool concentrations of #Butyrate, while #Acetate concentrations were increased.
  • - certain bacterial species, such as #Fusobacterium nucleatum, #Streptococcus bovis, and #Bacteroides fragilis have been linked to CRC, either by producing virulence factors or by producing pathogenic microbial metabolites.
  • [#Deoxycholic acid, #Secondary bile acids] - Elevated levels of fecal SBAs, especially DCA, are associated with an increased risk for CRC. - FXR, receptor for #Bile Acids, is downregulated in CRC and low levels of FXR expression correlate with worse clinic outcomes.
  • [#Hydrogen sulfide] - H2S increased the in vitro proliferation of human cells obtained from mucosal biopsies. - Interestingly, this effect was inhibited by #Butyrate.
  • - Plasma #Choline and #TMAO levels correlate with an increased risk for CRC and serum #TMAO levels are significantly increased in CRC patients.
  • [#Hydrogen sulfide] - #Fusobacterium nucleatum, a Gram negative, anaerobic bacterium over-represented in CRC tissues, is a H2S-producer. - F. nucleatum also produces the metabolite #Formate, which triggers AhR and increases cancer cell stemness and invasiveness.
  • [#Hydrogen sulfide] - Fecal H2S concentrations are elevated in CRC patients. - Increased levels of H2S can decrease tissue integrity by reducing disulfide bonds in mucosal tissues. - H2S can also directly cause DNA damage.
  • - #Indole derivates support gut homeostasis by promoting epithelial barrier function and immune tolerance, which are important to suppress carcinogenesis in the colon
  • - #Tryptophan metabolism is altered in CRC with a shift towards increased Kyn production by host cells but decreased #Indole production by gut microbes. - Elevated fecal Kyn to #Tryptophan ratios but decreased #Indole to tryptophane ratios were found in patients with colorectal neoplastic lesions.
  • [#kynurenine] - Kyn acts as an endogenous ligand for AhR and can be secreted by cancer cells into the tumor microenvironment, suppressing anti-tumor immunity and promoting tumor cell survival through AhR via autocrine and paracrine signaling.
  • [#Short Chain Fatty Acid] - GPR triggering by SCFAs is an important mechanism to suppress CRC development. - activation of GPRs on intestinal epithelial cells by SCFAs promotes barrier functions and stimulates the production of interleukin (IL)-18 and secretion of anti-microbial peptides.
  • [1.36] [#Parvimonas micra
    - grade 3 tumors Colorectal cancer were significantly enriched in #Fusobacterium and #Parvimonas - #Parvimonas micra and #Fusobacterium have been shown to aggregate and form biofilms in vitro. - Biofilm formation is linked to inflammatory bowel disease and CC.
  • [1.37] [#Obesity
  • [1.38
    - The elevated abundance of certain bacterial species such as #Fusobacterium nucleatum and #Parvimonas micra in CRC patients is often associated with the development of the disease.
  • [1.39] [#Inflamatory bowel disease
    - #Gemella enriches in the intestinal mucosa of IBD and CRC
  • [#Inflamatory bowel disease] [#Peptostreptococcus stomatis] - Regarding IBD and CRC, P. stomatis is among the oral-derived biomarker panel of CRC either
  • [#Natural oral microbiomes] [#Prevotella intermedia, #Prevotella nigrescens] - A higher abundance of P. intermedia and P. nigrescens (Pretovella species that are commonly resident in the oral cavity) was observed in the intestine of CRC patients
  • [#Periodontal abscess] [#Fusobacterium nucleatum] - patients with F. nucleatum or #Streptococcus pepticus bacteremia are more likely to suffer from subsequent colorectal cancer
  • [#Fusobacterium nucleatum] - 40% of the CRC patients detected identical F. nucleatum strains in both tumor tissue and saliva
  • [#Fusobacterium nucleatum] - Several F. nucleatum subspecies (nucleatum, animalis, vincentii, polymorphum) and potential new subspecies are isolated from the intestine of colorectal cancer patients, and the major encoding virulence factors for F. uncleatum showed evidence of horizontal gene transfer. - intraperitoneal injection successfully established colonization of F. nucleatum in CRC tissue, which suggested the translocation of F. nucleatum through hematogenous route
  • [#Fusobacterium nucleatum] - Regarding CRC, F. nucleatum and its main pathogenic factors (FadA (binding E-cadherin), Fap2 (a galactose-sensitive hemagglutinin and adhesin binding TIGHT receptors), RadD (autotransporter) and FomA) recruit tumor-infiltrating immune cells, generating tumor microenvironment and participating in immunosuppression and tumorigenesis
  • [#Porphyromonas gingivalis] [#Butyrate] - In the intestine, oral-derived microbiotas create an inflammatory and immunosuppressive microenvironment suitable for tumorigenesis. It is detected the existence of oral-originated bacteria (#Fusobacterium nucleatum, P. gingivalis, and #Parvimonas micra) in CRC tissues.
  • [#Porphyromonas gingivalis] - CRC patients’ intestines are pathologically colonized with abnormally abundant P. gingivalis, whose infection gives rise to a poor CRC prognosis
  • [#Porphyromonas gingivalis] - the #Peptidoglycan from P. gingivalis molecules induces programmed cell death 1 ligand 1 (PD-L1) up-regulation in colon carcinoma cells and mediates deep inhibition of T cells
  • - Analogous to the activity of #Niacin, #Butyrate activates GPR109A to suppress colonic inflammation and colon cancer development
  • [1.41
    - 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.

References Notes

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Common References