Fusobacterium ⇒ Fusobacterium nucleatum {10000137}

Shared Reference Notes

• [1.1] 
  - F. nucleatum and certain co-occurring bacteria were present not only in primary tumors but also in distant metastases. Preliminary evidence suggests that the bacterium is localized primarily within the metastatic #Cancer cells rather than in the stroma. - Antibiotic treatment of mice carrying xenografts of F. nucleatum–positive human colorectal #Cancer slowed tumor growth, consistent with a causal role for the bacterium in tumorigenesis.
• [1.2] [#Colorectal cancer] 
  - 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] [#Colorectal cancer] 
  - 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.
• [1.4] 
• [1.5] 
  - 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
• [1.6] [#Colorectal cancer] 
  - 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.
• [1.7] [#Colorectal cancer] 
  - 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
• [1.8] [#Alzheimer’s disease] [#Amyloid-beta, #Lipopolysaccharide] 
  - antibodies to F. nucleatum can be detected in the serum of patients with AD or cognitive impairment. - F. nucleatum activates microglial cells causing morphological changes, accelerated proliferation and enhanced expression of TNF-α and IL-1β in microglial cells. - LPS promoted the proliferation of brain microglia - F. nucleatum-induced periodontitis resulted in the exacerbation of Alzheimer’s symptoms in 5XFAD mice including increased cognitive impairment, beta-amyloid accumulation and Tau protein phosphorylation in the mouse cerebrum. - The stimnuli like LPS, Aβ or IFN-γ would activate microglial M1 phenotype, leading to the expression of pro-inflammatory cytokines and irreversible neuron loss. - The main known virulence factors of F. nucleatum include FadA, Fap2, and LPS
• [1.9] [#Hepatocellular cancer] 
  - Fusobacterium nucleatum was found to directly interact with TIGIT through the FAP2 protein, with subsequent inhibition of NK cells which have significant anti-tumor properties
• [#Cancer] - F. nucleatum subdue host immune response and triggers cellular proliferation.
• [1.11] [#Alzheimer’s disease] [#Amyloid-beta] 
  - Fusobacterium nucleatum can increased TNF-α and IL-1β expression in microglial cells, and also in vivo it can increase cognitive impairment, beta-amyloid accumulation and Tau protein phosphorylation in the cerebrum of an AD animal model.
• [1.12] [#Colorectal cancer] 
  - 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.
• [#Colorectal cancer] [#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.
• [1.13] [#Capnocytophaga gingivalis, #Tannerella forsythia, #Treponema denticola] 
  - Adverse pregnancy outcomes are a broad term containing preeclampsia, low birth weight, preterm premature rupture of membranes, early-onset neonatal sepsis, miscarriage, stillbirth, and fetal growth retardation - The prevalent oral species are #Filifactor alocis, Fusobacterium nucleatum, Porphyromonas gingivalis, #Campylobacter rectus, T. Denticola, and T. Forsythia, among others. - Stimulated fetal inflammatory and immune responses may ultimately increase the potential for Adverse pregnancy outcomes owing to the virulent properties assigned to microbiota in the intrauterine environment.
• [1.14] [#Colorectal cancer] 
  - 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.
• [1.15] [#CVD] 
  - Twenty-three bacterial species belonging to the subgingival plaque bacterial complexes were also identified in the blood of individuals from both the groups; Fusobacterium nucleatum was significantly less frequent in patients with CAD
• [1.16] [#Chronic periodontitis, #Periodontal disease] 
  - Chronic oral infection establishes ectopic oral F. nucleatum colonization in the intestine and significantly induces systemic humoral IgG and IgM antibody responses
• [#Colon adenomas, #Colon polyps] - F. nucleatum modifies colonic Th17 cell frequency and IL-17 expression recombinant free fatty acid receptor 2 (FFAR2)-dependent. - it positively correlated with the expression of Wnt-β-catenin (activated by FadA─E-cadherin) and REG Iα signaling, both of which effectively promotes the proliferation of sessile serrated adenoma/polyp
• [#Periodontal abscess] - patients with F. nucleatum or #Streptococcus pepticus bacteremia are more likely to suffer from subsequent #Colorectal cancer
• [#Colorectal cancer] - 40% of the CRC patients detected identical F. nucleatum strains in both tumor tissue and saliva
• - 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
• [#Colorectal cancer] - 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
• [#Colorectal cancer] [#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.
• - The continuum of its species and abundance in the GI tract could be an explanation. Transferring from saliva to the lower GI tract, the species diversity and abundance of F. nucleatum gradually dropped, indicating they resisted the selective stomach pressure
• - the TLR4-dependent mechanism promotes the M2 polarization of macrophages and immunosuppressive effect, suggesting that oral F. nucleatum evolves more powerful virulence after colonization
• - the TLR4-dependent mechanism promotes the M2 polarization of macrophages and immunosuppressive effect, suggesting that oral F. nucleatum evolves more powerful virulence after colonization. - Another virulence factor Fusobacterium produced that participates in immune regulation is the Fap2 protein, which directly interacts with TIGIT, mediates NK cell and T cell inhibition
• [#Inflamatory bowel disease] [#Clostridioides difficile] - F. nucleatum coexists with #Clostridium through adhesin RadD, encouraging the intestinal mucus layer’s bacterial biofilm formation in IBD patients. This symbiotic relationship accelerates the extracellular polysaccharides-producing process and chemotaxis level of C. difficile
• [#Periodontal disease] - successful periodontitis treatment reduces stool F. nucleatum levels

References Notes