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
• [1.17] [#Colorectal cancer] 
  - Fusobacterium nucleatum has been implicated as a carcinogen in #Oral squamous cell carcinoma (OSCC) and CRC, with a demonstrated bacterial transcript load 400 times that of matched adjacent normal tissue
• [1.18] 
  - Some oral #Bacteria (e.g., #Porphyromonas gingivalis, #Prevotella intermedia, #Aggregatibacter actinomycetemcomitans, and Fusobacterium nucleatum) produce volatile #Sulfur compounds (VSCs), such as #Hydrogen sulfide (H2S), methyl mercaptan (CH3SH), dimethyl #Sulfide ((CH3)2S), and dimethyl disulfide (CH3SSCH3).
• - A high abundance of #Fusobacterium (in particular F. nucleatum) at #Colorectal cancer sites has been associated with regional lymph node metastases and tumor location (2% in rectum and approx. 11% in cecum)
• [#IL-1b, #Lipopolysaccharide, #TNF-alfa] - Fusobacterium nucleatum LPS-activated inflammatory cytokines are include IL-1β, #IL-6, and TNF-α. The chronic inflammatory process leads to the loss of periodontal attachment and tissue damage
• [#Pancreatic Cancer] - In pancreatic cancers, in addition to Fusobacterium nucleatum and #Porphyromonas gingivalis, strains of #Aggregatibacter actinomycetemcomitans, #Neisseria elongata, and #Streptococcus mitis have been described.
• [1.19] 
  - #Cancer-associated bacteria are Fusobacterium nucleatum, #Peptostreptococcus stomatis, and #Parvimonas micra
• [#Breast cancer, #Pancreatic Cancer] - Fusobacterium nucleatum, previously reported to be enriched in colorectal tumors, was also a hit in our breast and pancreatic tumor cohorts
• [1.21] [#Colorectal cancer] 
  - Fusobacterium nucleatum has been shown to bind to host epithelial and endothelial cells through FadA adhesin and induce a series of inflammatory reactions mediated by Nuclear Factor-kappa B (NF-κB) and interleukin (IL)-6. - F. nucleatum abundance correlated with high #Glucose metabolism in patients with CRC. - F. nucleatum induces a dramatic decline of m6A modifications in CRC cells and patient-derived xenograft (PDX) tissues by downregulating an m6A methyltransferase, METTL3, contributing to the induction of CRC aggressiveness. - F. nucleatum can also inhibit the cytotoxic functions of tumor-infiltrating lymphocytes and natural killer (NK) cells by binding to the inhibitory immune receptor TIGIT through another adhesin, Fap2, thereby suppressing immune surveillance. - F. nucleatum may contribute to epithelial–mesenchymal transition (EMT), so it is tightly associated with cancer cell invasion, suppression of antitumor immune responses, stemness, and treatment resistance
• [1.22] [#Colorectal cancer] 
  - In CRC, infection of Fusobacterium nucleatum increases the expression of miR-21 and down-modulation of miR-18a and miR-4802 - Fusobacterium nucleatum enhanced tumor cell miR-21 levels by turning on the TLR4-MyD88 signaling cascade, which in turn increased CRC cell growth and tumor development in mice. - patients with high miR-21 and Fusobacterium nucleatum DNA levels consistently had a higher risk of negative outcomes. - Fusobacterium nucleatum enhances chemoresistance to CRC via changing autophagy in a way that is miRNA-dependen
• [1.23] 
  - #Fusobacticin-2 (produced by Fusobacterium nucleatum) from the oral microbiome has highly potent activity against the gut commensal #Eubacterium rectale.
• - the five most promising smORF-encoded peptides (SEPs) were encoded by diverse phyla from oral, skin, and gut body sites: #Faecalibacticin-3 (#Faecalibacterium prausnitzii), #Fusobacticin-2 (Fusobacterium nucleatum), #Keratinobacin-1 (#Keratinibaculum paraultunense), #Staphylococcin-2 (#Staphylococcus capitis), and #Prevotellin-2 (#Prevotella copri).
• [1.24] 
  - F. nucleatum was suggested to be enriched in #Cervical cancer and #Esophageal cancer compared to adjacent healthy tissue.
• [#Colorectal cancer, #Inflamatory bowel disease] - Intracellular F. nucleatum is also enriched in inflammatory bowel disease (IBD), a condition predisposing to CRC, especially in patients suffering from an active disease compared to those in remission.
• [#Colorectal cancer] [#Bacteroides fragilis, #Prevotella intermedia] - F. nucleatum-positive CRC tissues featured non-random co-colonization with commensals such as B. fragilis or P. intermedia, whereas tissues lacking F. nucleatum featured different bacterial colonization patterns
• [#Colorectal cancer] - lectin Fap2, expressed on F. nucleatum, binding to Gal-GalNAc on host cells. This interaction, in turn, drives an accumulation of Fusobacteria in CRC, upregulation of inflammatory markers upon invasion, and direct modulation of the TME
• [#Colorectal cancer] - CRC mouse model, increased tumor formation occurred upon gavage of F. nucleatum, while demonstrating a key role of FadA in its tumor-promoting activity
• [#Colorectal cancer] - An expansion of myeloid-derived immune cells including tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs) and myeloid-derived suppressor cells (MDSCs) in a F. nucleatum-inoculated CRC mouse model was accompanied by T-cell suppression and increased expression of immunosuppressive molecules such as CTLA4 and arginase-1
• [#Colorectal cancer] - 99.9% between F. nucleatum isolates from primary CRC and liver metastasis, indicating likely bacterial migratory characteristics between these tumor sites
• [#Colorectal cancer] - Higher intratumoral F. nucleatum abundance is associated with an increase in ALPK1, which in turn results in upregulation of intercellular adhesion molecule 1 (ICAM-1) on the host cell surface > increased attachment of CRC cells to endothelial cells > promote EMT and ultimately metastasis
• [#Colorectal cancer] - Keratin7 (KRT7) is reported to be upregulated in tumors upon F. nucleatum presence and was suggested to enhance lung metastasis in a murine CRC model
• [#Colorectal cancer] [#Porphyromonas gingivalis] - most CRC-associated microbes, such as F. nucleatum, P. gingivalis, and #Prevotella intermedia (P. intermedia) are suggested to reside intracellularly.
• [#Colorectal cancer] [#Antibiotic Therapy] - F. nucleatum-positive colorectal tumors were subcutaneously transplanted into immunodeficient mice and tracked over time. - viable F. nucleatum could be maintained over time, while antibiotic administration reduced tumor growth
• [#Colorectal cancer] [#Antibiotic Therapy] - antibiotic treatment of mice transplanted with F. nucleatum-positive patient-derived CRC xenografts reduces tumor size and cancer cell proliferation, indicating that bacterial suppression may support tumor growth suppression
• [#Colorectal cancer] [#Bacteriophage] - phages targeting F. nucleatum, combined with irinotecan were able to reduce tumor growth, while selectively inhibiting CRC-associated bacterium F. nucleatum in vivo
• [#Colorectal cancer] - F. nucleatum is suggested to enhance CRC progression through its FadA adhesin, which attaches to epithelial cadherin (#E-cadherin) and may activate the Wnt/β-catenin signaling pathway86 leading to enhanced proliferation
• [#Colorectal cancer] [#Short Chain Fatty Acid] - F. nucleatum-derived short-chain fatty acid #Formate > CRC cell stemness and invasion
• - interaction of Fap2, expressed by F. nucleatum, with the human inhibitory receptor T-cell immunoreceptor with Ig and ITIM domains (TIGIT) expressed on immune cells such as NK cells and T cells, abrogated NK cell-mediated killing of human tumor cells. - F. nucleatum-induced Fap2-dependent mechanisms can drive lymphocyte apoptosis
• [#Porphyromonas gingivalis] - communities containing both F. nucleatum and P. gingivalis featured a higher rate of invasion of gingival epithelial cells as compared to those featuring either of these species without the othe
• [#Porphyromonas gingivalis] - F. nucleatum can bind to the salivary protein statherin via FomA, which functions in biofilm formation and is known to bind especially to P. gingivalis
• [1.25] [#Colorectal cancer] 
  - Cancer of the colon-associated bacterium F. nucleatum can specifically inhibit antitumor immunity by involving certain T cells, immunoglobulin receptor cells, and natural killer cells, and by preventing its ability to damage tumor cells
• [#Colorectal cancer] - F. nucleatum can protect tumor cells from antitumor agents, which leads to chemotherapy resistance in CRC patients.
• - Fusobacterium adhesin A (FadA) of F. nucleatum interacts with E-cadherins which in turn activate the signaling of Wnt/β-catenin and may induce proliferation and tumorigenesis.
• F. nucleatum additionally inhibits the action of T cells plus NK, which limits their ability to combat adenocarcinoma in the colon.
• [#Antibiotic Therapy] - mice experiments have shown that antibiotic use suppresses F. nucleatum significantly increases #Chemotherapy efficacy
• [1.26] [#Porphyromonas gingivalis, #Prevotella intermedia, #Tannerella forsythia, #Treponema denticola] 
  - P. gingivalis, T. denticola, T. forsythia, P. intermedia, F. nucleatum and #Filifactor alocis are traditionally recognized as major pathogens responsible for #Periodontal disease
• [1.27] [#Colorectal cancer] 
  - #Methanethiol as a biomarker for non-invasive early #Cancer detection. - Commensal #Bacteria residing in the colonic lumen can convert dietary #Methionine to #Methanethiol through MGL-catalyzed α,γ-elimination and γ-replacement reactions. - Fusobacterium nucleatum, #Citrobacter freundii, #Morganella morganii,and several #Proteus species have been reported to contribute to intestinal #Methanethiol production
• [1.28] 
  - The dominant species identified in the bile of #Gallbladder cancer patients included Fusobacterium nucleatum, #Escherichia coli, and #Enterobacter sp., while the bile from cholelithiasis patients primarily contained #Escherichia coli, #Salmonella sp., and #Enterococcus gallinarum
• [1.29] [#Colorectal cancer] 
  - F. nucleatum was associated with MMRd related to Lynch syndrome as well as sporadic MMRd CRCs related to MLH1 promoter methylation and double MMR somatic mutations. - F. nucleatum colonisation in the tumour is not related to MMRd etiology. - F. nucleatum causing opportunistic infections, exploiting the specific tumour microenvironment of MMRd CRCs. - F. nucleatum is found to be highly abundant in CRC tumours
• [#Diabetes Type 2] [#Porphyromonas gingivalis, #Prevotella intermedia] - mice fed a high-fat diet, combined administration of P. gingivalis, F. nucleatum, and P. intermedia induced impaired blood #Glucose metabolism and insulin resistance with concomitant changes in the gut microbial composition.
• [#Porphyromonas gingivalis, #Treponema denticola] - #Nisin has concentration-dependent antimicrobial activity against Gram-negative periodontopathic bacteria such as P.gingivalis, T.denticola, and F.nucleatum
• [1.31] [#Candida albicans] 
  - F. nucleatum and C. albicans co-aggregate by interacting between genetic and morphological cellular elements
• [#Candida albicans, #Streptococcus oralis] - The ability of C. albicans to form alliances with F. nucleatum, circumventing host defenses, and its interaction with #Streptococcus mutans, or S. oralis to exacerbate oral candidiasis or dental #Caries
• [1.32] 
  - Fusobacterium nucleatum species are normal members of the human oral microbiota, and strains from the oral cavity are thought to seed CRC tumours. - Fna is bifurcated into two distinct clades: Fna C1, which is largely restricted to the oral cavity, and Fna C2, which dominates the human CRC tumour niche. - Only Fna C2 induced tumours and altered intestinal metabolism towards increased oxidative stress within a CRC animal model. - The analysis revealed 195 genetic differences between the clades. - this Fna C2 lineage in approximately 50% of cases. - Fna C2 levels were consistently higher in #Colorectal cancer.
• [#Colorectal cancer] - patients with colorectal tumors containing Fusobacterium nucleatum have poor survival and poorer prognosis compared with patients without the microbe
• [1.33] [#Diabetes Type 2] 
  - oral Fusobacterium nucleatum and gut #Lactobacillus are increased in in diabetic coronary heart disease (DCHD) patients, with a positive correlation between the two. - in hyperglycemic mice, augmented Fusobacterium nucleatum levels in the oral cavity were accompanied by an imbalance in the oral-gut axis, characterized by an increased coexistence of Fusobacterium nucleatum and #Lactobacillus, along with elevated cardiac miRNA-21 and a greater extent of myocardial damage
• [1.34] [#Oral squamous cell carcinoma] 
  - oral cavity squamous cell carcinoma (OSCC) > enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, #Treponema medium, #Peptostreptococcus stomatis, #Gemella morbillorum, #Catonella morbi, #Peptoanaerobacter yurli and #Peptococcus simiae) were observed in OSCC tumor microenvironment. - pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations.
• [#Oral squamous cell carcinoma] - oral cavity squamous cell carcinoma (OSCC) > Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with #E-cadherin/β-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT).
• [1.35] [#Colorectal cancer] [#Teenager] 
  - well-known CRC-associated taxa, such as #Clostridium symbiosum, #Peptostreptococcus stomatis, #Parvimonas micra and #Hungatella hathewayi were significantly enriched in both old- and young-onset patients. - Similar strain-level patterns of Fusobacterium nucleatum, #Bacteroides fragilis and #Escherichia coli were observed for oCRC and yCRC. - Almost all oCRC-associated metagenomic pathways had directionally concordant changes in young patients.
• [1.36] [#Colorectal cancer] 
  - Fusobacterium nucleatum, did not significantly associate with CRC diagnostic groups (healthy, adenoma and carcinoma) when controlling for covariates transit time, fecal #Calprotectin (intestinal inflammation) and body mass index as primary microbial covariates. - In contrast, the associations of #Anaerococcus vaginalis, #Dialister pneumosintes, #Parvimonas micra, #Peptostreptococcus anaerobius, #Porphyromonas asaccharolytica and #Prevotella intermedia remained robust, highlighting their future target potential.
• [1.37] [#Colorectal cancer] [#Escherichia coli] 
  - in CRC > M1 macrophages promote cytotoxicity and effectuate a tumor-suppressive microenvironment while M2 macrophages are associated with immunosuppression and the expression of cytokines that promote tumor survival and proliferation. - Both E. coli and F. nucleatum have been shown to shift this balance in favor of the M2 state.
• [#Colorectal cancer] - F. nucleatum-derived succinic acid confers resistance to anti-PD-1 therapy, reversible by fecal microbiota transfer or #Metronidazole.

References Notes