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Nature Reviews. Microbiology Mar 2019Fusobacterium nucleatum has long been found to cause opportunistic infections and has recently been implicated in colorectal cancer; however, it is a common member of... (Review)
Review
Fusobacterium nucleatum has long been found to cause opportunistic infections and has recently been implicated in colorectal cancer; however, it is a common member of the oral microbiota and can have a symbiotic relationship with its hosts. To address this dissonance, we explore the diversity and niches of fusobacteria and reconsider historic fusobacterial taxonomy in the context of current technology. We also undertake a critical reappraisal of fusobacteria with a focus on F. nucleatum as a mutualist, infectious agent and oncogenic microorganism. In this Review, we delve into recent insights and future directions for fusobacterial research, including the current genetic toolkit, our evolving understanding of its mechanistic role in promoting colorectal cancer and the challenges of developing diagnostics and therapeutics for F. nucleatum.
Topics: Carcinogenesis; Colorectal Neoplasms; Fusobacterium Infections; Fusobacterium nucleatum; Host Microbial Interactions; Humans; Mouth; Symbiosis
PubMed: 30546113
DOI: 10.1038/s41579-018-0129-6 -
Gut Microbes 2023The etiology of colorectal cancer (CRC) is influenced by bacterial communities that colonize the gastrointestinal tract. These microorganisms derive essential nutrients... (Review)
Review
The etiology of colorectal cancer (CRC) is influenced by bacterial communities that colonize the gastrointestinal tract. These microorganisms derive essential nutrients from indigestible dietary or host-derived compounds and activate molecular signaling pathways necessary for normal tissue and immune function. Associative and mechanistic studies have identified bacterial species whose presence may increase CRC risk, including notable examples such as , Enterotoxigenic , and pks . In recent years this work has expanded in scope to include aspects of host mutational status, intra-tumoral microbial heterogeneity, transient infection, and the cumulative influence of multiple carcinogenic bacteria after sequential or co-colonization. In this review, we will provide an updated overview of how host-bacteria interactions influence CRC development, how this knowledge may be utilized to diagnose or prevent CRC, and how the gut microbiome influences CRC treatment efficacy.
Topics: Humans; Colorectal Neoplasms; Escherichia coli; Gastrointestinal Microbiome; Fusobacterium nucleatum; Bacterial Infections
PubMed: 36927206
DOI: 10.1080/19490976.2023.2185028 -
Periodontology 2000 Jun 2022Accumulating evidence demonstrates that the oral pathobiont Fusobacterium nucleatum is involved in the progression of an increasing number of tumors types. Thus far, the... (Review)
Review
Accumulating evidence demonstrates that the oral pathobiont Fusobacterium nucleatum is involved in the progression of an increasing number of tumors types. Thus far, the mechanisms underlying tumor exacerbation by F. nucleatum include the enhancement of proliferation, establishment of a tumor-promoting immune environment, induction of chemoresistance, and the activation of immune checkpoints. This review focuses on the mechanisms that mediate tumor-specific colonization by fusobacteria. Elucidating the mechanisms mediating fusobacterial tumor tropism and promotion might provide new insights for the development of novel approaches for tumor detection and treatment.
Topics: Fusobacterium Infections; Fusobacterium nucleatum; Humans; Neoplasms
PubMed: 35244982
DOI: 10.1111/prd.12426 -
Trends in Microbiology Feb 2023Colorectal cancer (CRC), one of the most prevalent cancers, has complex etiology. The dysbiosis of intestinal bacteria has been highlighted as an important contributor... (Review)
Review
Colorectal cancer (CRC), one of the most prevalent cancers, has complex etiology. The dysbiosis of intestinal bacteria has been highlighted as an important contributor to CRC. Fusobacterium nucleatum, an oral anaerobic opportunistic pathogen, is enriched in both stools and tumor tissues of patients with CRC. Therefore, F. nucleatum is considered to be a risk factor for CRC. This review summarizes the biological characteristics and the mechanisms underlying the regulatory behavior of F. nucleatum in the tumorigenesis and progression of CRC. F. nucleatum as a marker for the early warning and prognostic prediction of CRC, and as a target for prevention and treatment, is also described.
Topics: Humans; Fusobacterium nucleatum; Colorectal Neoplasms; Virulence Factors; Biomarkers; Carcinogenesis
PubMed: 36058786
DOI: 10.1016/j.tim.2022.08.010 -
Current Opinion in Microbiology Feb 2015Fusobacterium nucleatum is an anaerobic oral commensal and a periodontal pathogen associated with a wide spectrum of human diseases. This article reviews its implication... (Review)
Review
Fusobacterium nucleatum is an anaerobic oral commensal and a periodontal pathogen associated with a wide spectrum of human diseases. This article reviews its implication in adverse pregnancy outcomes (chorioamnionitis, preterm birth, stillbirth, neonatal sepsis, preeclampsia), GI disorders (colorectal cancer, inflammatory bowel disease, appendicitis), cardiovascular disease, rheumatoid arthritis, respiratory tract infections, Lemierre's syndrome and Alzheimer's disease. The virulence mechanisms involved in the diseases are discussed, with emphasis on its colonization, systemic dissemination, and induction of host inflammatory and tumorigenic responses. The FadA adhesin/invasin conserved in F. nucleatum is a key virulence factor and a potential diagnostic marker for F. nucleatum-associated diseases.
Topics: Bacteria, Anaerobic; Cell Transformation, Neoplastic; Female; Fusobacterium Infections; Fusobacterium nucleatum; Humans; Inflammation; Male; Pregnancy; Pregnancy Complications, Infectious; Virulence; Virulence Factors
PubMed: 25576662
DOI: 10.1016/j.mib.2014.11.013 -
Cell Host & Microbe May 2023Rheumatoid arthritis (RA) is an autoimmune disorder that has been associated with the gut microbiota. However, whether and how the gut microbiota plays a pathogenic role...
Rheumatoid arthritis (RA) is an autoimmune disorder that has been associated with the gut microbiota. However, whether and how the gut microbiota plays a pathogenic role in RA remains unexplored. Here, we observed that Fusobacterium nucleatum is enriched in RA patients and positively associated with RA severity. F. nucleatum similarly aggravates arthritis in a mouse model of collagen-induced arthritis (CIA). F. nucleatum outer membrane vesicles (OMVs) containing the virulence determinant FadA translocate into the joints, triggering local inflammatory responses. Specifically, FadA acts on synovial macrophages, resulting in the activation of the Rab5a GTPase involved in vesicle trafficking and inflammatory pathways and YB-1, a key regulator of inflammatory mediators. OMVs containing FadA and heightened Rab5a-YB-1 expression were observed in RA patients compared with controls. These findings suggest a causal role of F. nucleatum in aggravating RA and provide promising therapeutic targets for clinically ameliorating RA.
Topics: Animals; Mice; Fusobacterium nucleatum; Virulence Factors; Arthritis, Rheumatoid
PubMed: 37054714
DOI: 10.1016/j.chom.2023.03.018 -
BMC Cancer Nov 2021There is a growing level of interest in the potential role inflammation has on the initiation and progression of malignancy. Notable examples include Helicobacter... (Review)
Review
There is a growing level of interest in the potential role inflammation has on the initiation and progression of malignancy. Notable examples include Helicobacter pylori-mediated inflammation in gastric cancer and more recently Fusobacterium nucleatum-mediated inflammation in colorectal cancer. Fusobacterium nucleatum is a Gram-negative anaerobic bacterium that was first isolated from the oral cavity and identified as a periodontal pathogen. Biofilms on oral squamous cell carcinomas are enriched with anaerobic periodontal pathogens, including F. nucleatum, which has prompted hypotheses that this bacterium could contribute to oral cancer development. Recent studies have demonstrated that F. nucleatum can promote cancer by several mechanisms; activation of cell proliferation, promotion of cellular invasion, induction of chronic inflammation and immune evasion. This review provides an update on the association between F. nucleatum and oral carcinogenesis, and provides insights into the possible mechanisms underlying it.
Topics: Animals; Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Fusobacterium Infections; Fusobacterium nucleatum; Humans; Immune Evasion; Immunity, Cellular; Inflammation; Metronidazole; Mice; Mouth Neoplasms; Neoplasm Invasiveness; Porphyromonas gingivalis; Squamous Cell Carcinoma of Head and Neck
PubMed: 34774023
DOI: 10.1186/s12885-021-08903-4 -
Periodontology 2000 Jun 2022The link between oral health and adverse pregnancy outcomes has been suggested by numerous epidemiological studies. More recent studies indicate the relationship between... (Review)
Review
The link between oral health and adverse pregnancy outcomes has been suggested by numerous epidemiological studies. More recent studies indicate the relationship between severity of periodontal disease and adverse pregnancy outcomes. Two virulence mechanisms are proposed: direct invasion of oral microorganisms or their components into the fetal-placenta unit and inflammatory mediators produced in the oral cavity affecting the fetal-placenta unit. While interventional periodontal therapy still yielded contradictory results, animal studies suggest that maternal supplementation of omega-3 fatty acids protects the fetus by suppressing inflammation as well as bacteria proliferation in the placenta. This article reviews the recent epidemiological, mechanistic, interventional, and therapeutic studies of oral health and adverse pregnancy outcomes.
Topics: Animals; Female; Fusobacterium nucleatum; Humans; Oral Health; Periodontal Diseases; Porphyromonas gingivalis; Pregnancy; Pregnancy Outcome
PubMed: 35244963
DOI: 10.1111/prd.12436 -
Cell Communication and Signaling : CCS Dec 2022Z-DNA binding protein 1 (ZBP1) is a vital innate immune sensor that regulates inflammation during pathogen invasion. ZBP1 may contribute to pyroptosis, apoptosis and...
BACKGROUND
Z-DNA binding protein 1 (ZBP1) is a vital innate immune sensor that regulates inflammation during pathogen invasion. ZBP1 may contribute to pyroptosis, apoptosis and necroptosis in infectious diseases. In this study, Fusobacterium nucleatum (F. nucleatum) infection caused periapical inflammation through proinflammatory cell death and ZBP1 was involved in regulating the inflammatory activities caused by F. nucleatum infection in apical periodontitis (AP).
METHODS
Human periapical tissues were tested by fluorescent in situ hybridization, immunohistochemical staining, immunofluorescence staining, quantitative real-time PCR (qRT‒PCR) and western blotting. F. nucleatum-infected and F. nucleatum extracellular vesicles (F. nucleatum-EVs)-treated RAW264.7 cells were used to detect the expression of inflammatory cytokines and different cell death mechanisms by qRT‒PCR and western blotting. ZBP1 expression in F. nucleatum-infected tissues and RAW264.7 cells was detected by qRT‒PCR, western blotting, and immunohistochemical and immunofluorescence staining. Furthermore, the expression of ZBP1 was inhibited by siRNA and different cell death pathways, including pyroptosis, apoptosis, and necroptosis, and inflammatory cytokines were measured in F. nucleatum-infected RAW264.7 cells.
RESULTS
F. nucleatum was detected in AP tissues. F. nucleatum-infected RAW264.7 cells polarized to the M1 phenotype, and this was accompanied by inflammatory cytokine production. High levels of ZBP1 and GSDME (gasdermin E)-mediated pyroptosis, caspase-3-mediated apoptosis and MLKL-mediated necroptosis (PANoptosis) were identified in F. nucleatum-infected tissues and RAW264.7 cells. ZBP1 inhibition reduced inflammatory cytokine secretion and the occurrence of PANoptosis.
CONCLUSION
The present study identified a previously unknown role of ZBP1 in regulating F. nucleatum-induced proinflammatory cell death and inflammatory activation. Video abstract.
Topics: Humans; Fusobacterium nucleatum; In Situ Hybridization, Fluorescence; Cell Death; Inflammation; Cytokines; Periapical Periodontitis; DNA-Binding Proteins
PubMed: 36539813
DOI: 10.1186/s12964-022-01005-z -
Current Protein & Peptide Science 2017There is growing recognition that composition and metabolic activity of the gut microbiota can be modulated by the dietary proteins which in turn impact health. The... (Review)
Review
There is growing recognition that composition and metabolic activity of the gut microbiota can be modulated by the dietary proteins which in turn impact health. The amino acid composition and digestibility of proteins, which are influenced by its source and amount of intake, play a pivotal role in determining the microbiota. Reciprocally, it appears that the gut microbiota is also able to affect protein metabolism which gives rise to the view that function between the microbiota and protein can proceed in both directions. In response to the alterations in dietary protein components, there are significant changes in the microbial metabolites including short chain fatty acids (SCFAs), ammonia, amines, gases such as hydrogen, sulfide and methane which are cytotoxins, genotoxins and carcinogens associated with development of colon cancer and inflammatory bowel diseases. A suitable ratio between protein and carbohydrate or even a low protein diet is recommended based on the evidence that excessive protein intake adversely affects health. Supplying high and undigested proteins will encourage pathogens and protein-fermenting bacteria to increase the risk of diseases. These changes of microbiota can affect the gut barrier and the immune system by regulating gene expression in relevant signaling pathways and by regulating the secretion of metabolites. The objective of this review is to assess the impact of dietary proteins on microbiota composition and activity in the gastrointestinal tract. Attention should be given to the dietary strategies with judicious selection of source and supplementation of dietary protein to benefit gut health.
Topics: Actinobacteria; Amines; Ammonia; Bacteroidetes; Dietary Carbohydrates; Dietary Proteins; Fatty Acids, Volatile; Fermentation; Firmicutes; Fusobacteria; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Proteobacteria; Proteolysis; Verrucomicrobia
PubMed: 28215168
DOI: 10.2174/1389203718666170216153505