Application of Fusobacterium nucleatum as a biomarker in gastrointestinal malignancies

The morbidity and mortality of gastrointestinal(GI)malignancies are among the highest in the world,posing a serious threat to human health.Because of the insidious onset of the cancer,it is difficult for patients to be diagnosed at an early stage,and it rapidly progresses to an advanced stage,resulting in poor treatment and prognosis.Fusobacterium nucleatum(F.nucleatum)is a gram-negative,sporefree anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal,esophageal,gastric,and pancreatic cancers via various intricate mechanisms.Recent development in novel research suggests that F.nucleatum may function as a biomarker in GI malignancies.Detecting the abundance of F.nucleatum in stool,saliva,and serum samples of patients may aid in the diagnosis,risk assessment,and prognosis monitoring of GI malignancies.This editorial systematically describes the biological roles and mechanisms of F.nucleatum in GI malignancies focusing on the application of F.nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F.nucleatum and GI tumors-related research.

Fusobacterium nucleatum-induced imbalance in microbiome-derived butyric acid levels promotes the occurrence and development of colorectal cancer

BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignant tumors globally.Recent reports suggest that Fusobacterium nucleatum(F.nucleatum)contributes to the initiation,progression,and prognosis of CRC.Butyrate,a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber,is known to inhibit various cancers.This study is designed to explore whether F.nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid.AIM To investigate the mechanism by which F.nucleatum affects CRC occurrence and development.METHODS Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F.nucleatum.Additionally,DLD-1 and HCT116 cell lines were exposed to sodium butyrate(NaB)and F.nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function.RESULTS Our research indicates that the prevalence of F.nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts,while the prevalence of butyrate-producing bacteria is notably lower.In mice colonized with F.nucleatum,the population of butyrate-producing bacteria decreased,resulting in altered levels of butyric acid,a key intestinal metabolite of butyrate.Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells.Consequently,this leads to modulated production of adenosine triphosphate and reactive oxygen species,thereby inhibiting cancer cell prolif-eration.Additionally,NaB triggers the adenosine monophosphate-activated protein kinase(AMPK)signaling pathway,blocks the cell cycle in HCT116 and DLD-1 cells,and curtails the proliferation of CRC cells.The combined presence of F.nucleatum and NaB attenuated the effects of the latter.By employing small interfering RNA to suppress AMPK,it was demonstrated that AMPK is essential for NaB’s inhibition of CRC cell proliferation.CONCLUSION F.nucleatum can promote cancer progression through its inhibitory effect on butyric acid,via the AMPK signaling pathway.

Structural and Functional Annotation of Hypothetical Protein of Fusobacterium nucleatum Strain MJR7757B: An in Silico Approach

Fusobacterium nucleatum is an anaerobic, commensal, gram-negative oral bacterium that is carcinogenic and causes a wide range of human diseases. The present study focused on the analysis of the hypothetical protein, HMPREF3221_01179, derived from F. nucleatum strain MJR7757B, employing various computational methods to anticipate both its structure and functional characteristics. NCBI conserved domain analysis, NCBI BLASTp and MEGA Phylogenetic tree study characterize the target protein as an outer membrane efflux protein (ToIC family) which facilitate the bacterial transmembrane transport. With a molecular weight of 52120.02 Da, an isoelectric point (pI) of 8.33, and an instability index of 29.47, the protein is anticipated to exhibit good solubility in the extracellular space and crucial stability for pharmaceutical applications. The protein’s structure meets quality standards during the construction and refinement of its 3D model. The efflux inhibitor Arginine beta-naphthylamide exhibits a significant binding affinity (-7.1 kcal/mol) to the binding site of the target protein. The in-silico analysis improves the understanding of the protein and facilitates future investigations into therapeutic medication.

The Diagnostic Value of Fecal Fusobacterium nucleatum Combined with FIT and CA199 in the Diagnosis of Colorectal Cancer

Objective:To analyze the diagnostic value of fecal Fusobacterium nucleatum detection,fecal immunochemical test(FIT),and carbohydrate antigen 19-9(CA19-9)detection for colorectal cancer(CRC).Method:Atotal of 78 CRC patients and 60 healthy individuals were enrolled in this study.Stool and blood samples were collected for the 3 diagnoses,and ROC curves were analyzed for diagnostic value.Result:The 3 diagnoses’positive detection rates in CRC samples were significantly higher than those of healthy samples(P<0.05).The combined CRC diagnoses showed significantly higher sensitivity as compared to individual fecal F.nucleatum detection(χ^(2)=6.495,P=0.011),FIT(χ^(2)=4.871,P=0.027),and serum CA19-9 detection(χ^(2)=7.371,P=0.007).The area under the ROC curve for fecal F.nucleatum detection was 0.63[95%confidence interval(CI)=1.124–6.238],with a sensitivity of 73.08%and specificity of 85.00%,whereas FIT was 0.65(95%CI=1.365–9.241),with a sensitivity of 51.28%and specificity of 96.67%,meanwhile,serum CA19-9 detection was 0.62(95%CI=1.517–12.342),with a sensitivity of 69.23%and specificity of 98.33%.The combined CRC diagnoses showed an area under the ROC curve of 0.76(95%CI=1.213–6.254),with a sensitivity of 87.18%and specificity of 70.00%.Conclusion:The combined diagnoses of fecal F.nucleatum detection,FIT,and serum CA19-9 detection can significantly improve the sensitivity and accuracy of CRC diagnosis,which has high clinical application value to provide guidance for clinical CRC screening and early intervention treatment.

One Step Multiplex PCR for Identifications at Subspecies Level of Fusobacterium nucleatum and Fusobacterium necrophorum

Purpose: Fusobacterium nucleatum is an opportunistic pathogen involved in periodontal diseases, extraoral infections, and colorectal cancer. Fusobacterium necrophorum causes a variety of necrotic infections. F. nucleatum and F. necrophorum are classified into five and two subspecies, respectively. Conventional identification methods were technically hard to distinguish each subspecies of two Fusobacterium species accurately. The purpose of the present study was to design primers to identify two medically important Fusobacterium species at the subspecies level, using one-step multiplex PCR. Methods: Polymerase chain reaction (PCR) primers were designed based on partial sequences of the 16S ribosomal RNA (16S rRNA) gene, RNA polymerase B (rpoB) gene, and DNA gyrase subunit B (gyrB) of each subspecies of F. nucleatum and F. necrophorum. Results: These primers were able to distinguish each subspecies of F. nucleatum and F. necrophorum and did not display cross-reactivity with representative Fusobacterium species other than F. nucleatum and F. necrophorum. Conclusion: Our developed one-step multiplex PCR method is accurate, specific, cost-effective, time-saving, and worked without requiring DNA extraction.

Association of Fusobacterium nucleatum with immunity andmolecular alterations in colorectal cancer

The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6%(44/511), which was lower than that in United States cohort studies(13%). Similar to the United States studies, F. nucleatum positivityin Japanese colorectal cancers was significantly associated with microsatellite instability(MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets(i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain micro RNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. Micro RNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may provide insights for strategies to target microbiota, immune cells and tumor molecular alterations for colorectal cancer prevention and treatment. Further investigation is needed to clarify the association of Fusobacterium with T-cells and micro RNA expressions in colorectal cancer.

Association of Fusobacterium nucleatum infection with colorectal cancer in Chinese patients

AIM: To investigate Fusobacterium nucleatum(F. nucleatum) abundance in colorectal cancer(CRC) tissues and its association with CRC invasiveness in Chinese patients.METHODS: The resected cancer and adjacent normal tissues(10 cm beyond cancer margins) from 101 consecutive patients with CRC were collected. Fluorescent quantitative polymerase chain reaction(FQ-PCR) was applied to detect F. nucleatum in CRC and normal tissues. The difference of F. nucleatum abundance between cancer and normal tissues and the relationship of F. nucleatum abundance with clinical variables were evaluated. Fluorescence in situ hybridization(FISH) analysis was performed on 22 CRC tissues with the highest F. nucleatum abundance by FQ-PCR testing to confirm FQ-PCR results.RESULTS: The median abundance of F. nucleatum in CRC tissues [0.242(0.178-0.276)] was significantly higher than that in normal controls [0.050(0.023-0.067)](P < 0.001). F. nucleatum was over-represented in 88/101(87.1%) CRC samples. The abundance of F. nucleatum determined by 2^(-ΔCT) was significantly greater in tumor samples [0.242(0.178, 0.276)] than in normal controls [0.050(0.023, 0.067)](P < 0.001). The frequency of patients with lymph node metastases was higher in the over-abundance group [52/88(59.1%)] than in the under-abundance group [0/13(0%)](P < 0.005). No significant association of F. nucleatum with other clinico-pathological variables was observed(P > 0.05). FISH analysis also found more F. nucleatum in CRC than in normal tissues(median number 6, 25^(th) 3, 75^(th) 10 vs 2, 25^(th) 1, 75^(th) 5)(P < 0.01).CONCLUSION: F. nucleatum was enriched in CRC tissues and associated with CRC development and metastasis.

Fusobacterium 's link to colorectal neoplasia sequenced: A systematic review and future insights

AIM To critically evaluate previous scientific evidence on Fusobacterium's role in colorectal neoplasia development.METHODS Two independent investigators systematically reviewed all original scientific articles published between January,2000,and July,2017,using Pub Med,EMBASE,and MEDLINE. A total of 355 articles were screened at the abstract level. Of these,only original scientific human,animal,and in vitro studies investigating Fusobacterium and its relationship with colorectal cancer(CRC) were included in the analysis. Abstracts,review articles,studies investigating other colonic diseases,and studies written in other languages than English were excluded from our analysis. Ninety articles were included after removing duplicates,resolving disagreements between the two reviewers,and applying the above criteria.RESULTS Studies have consistently identified positive associations between Fusobacterium,especially Fusobacterium nucleatum(F. nucleatum),and CRC. Stronger associations were seen in CRCs proximal to the splenic flexure and Cp G island methylator phenotype(CIMP)-high CRCs. There was evidence of temporality and a biological gradient,with increased F. nucleatum DNA detection and quantity along the traditional adenoma-carcinoma sequence and in CIMP-high CRC precursors. Diet may have a differential impact on colonic F. nucleatum enrichment;evidence suggests that high fiber diet may reduce the risk of a subset of CRCs that are F. nucleatum DNA-positive. Data also suggest shorter CRC and disease-specific survival with increased amount of F. nucleatum DNA in CRC tissue. The pathophysiology of enrichment of F. nucleatum and other Fusobacterium species in colonic tissue is unclear;however,the virulence factors and changes to the local colonic environment with disruption of the protective mucus layer may contribute. The presence of a host lectin(Gal-Gal NAc) in the colonic epithelium may also mediate F. nucleatum attachment to CRC and precursors through interaction with an F. nucleatum protein,fibroblast activation protein 2(FAP2). The clinical significance of detection or enrichment of Fusobacterium in colorectal neoplasia is ambiguous,but data suggest a procarcinogenic effect of F. nucleatum,likely due to activation of oncogenic and inflammatory pathways and modulation of the tumor immune environment. This is hypothesized to be mediated by certain F. nucleatum strains carrying invasive properties and virulence factors such as Fad A and FAP.CONCLUSION Evidence suggests a potential active role of Fusobacterium,specifically F. nucleatum,in CRC. Future prospective and experimental human studies would fill an important gap in this literature.

Fusobacterium nucleatum and colorectal cancer:A review

Fusobacterium nucleatum (F.nucleatum) is a Gramnegative obligate anaerobe bacterium in the oral cavity and plays a role in several oral diseases, including periodontitis and gingivitis. Recently, several studies have reported that the level of F.nucleatum is significantly elevated in human colorectal adenomas and carcinomas compared to that in adjacent normal tissue. Several researchers have also demonstrated that F.nucleatum is obviously associated with colorectal cancer and promotes the development of colorectal neoplasms. In this review, we have summarized the recent reports on F.nucleatum and its role in colorectal cancer and have highlighted the methods of detecting F.nucleatum in colorectal cancer, the underlying mechanisms of pathogenesis, immunity status, and colorectal cancer prevention strategies that target F.nucleatum.

Relationship between Fusobacterium nucleatum,inflammatory mediators and microRNAs in colorectal carcinogenesis

AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.

Pyogenic liver abscess caused by Fusobacterium in a 21-year-old immunocompetent male

A 21-year-old male with no significant past medical history, presented with right upper quadrant(RUQ) abdominal pain along with fevers and chills. Lab work revealed leukocytosis, anemia, and slightly elevated alkaline phosphatase. Viral serology for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus were negative and he was immunocompetent.Computed tomography imaging revealed hepatic abscesses, the largest measuring 9.5 cm. Empiric antibiotics were started and percutaneous drains were placed in the abscesses. Anaerobic cultures from the abscesses grew Fusobacterium nucleatum. This is a gram negative anaerobic bacteria; a normal flora of the oral cavity. Fusobacterium is most commonly seen in Lemiere's disease, which is translocation of oral bacteria to the internal jugular vein causing a thrombophlebitis and subsequent spread of abscesses. Our patient did not have Lemiere's, and is the first case described of fusobacterium pyogenic liver abscess in a young immunocompetent male with good oral hygiene. This case was complicated by sepsis, empyema, and subsequent abscesses located outside the liver. These abscesses' have the propensity to flare abruptly and can be fatal. This case not only illustrates fusobacterium as a rare entity for pyogenic liver abscess, but also the need for urgent diagnosis and treatment. It is incumbent on physicians to diagnose and drain any suspicious hepatic lesions. While uncommon, such infections may develop without any overt source and can progress rapidly. Prompt drainage with antibiotic therapy remains the cornerstone of therapy.

Fusobacterium nucleatum colonization is associated with decreased survival of helicobacter pylori-positive gastric cancer patients

BACKGROUND An increased amount of Fusobacterium nucleatum(F.nucleatum)is frequently detected in the gastric cancer-associated microbiota of the Taiwan Residents population.F.nucleatum is known to exert cytotoxic effects and play a role in the progression of colorectal cancer,though the impact of F.nucleatum colonization on gastric cancer cells and patient prognosis has not yet been examined.AIM To identify F.nucleatum-dependent molecular pathways in gastric cancer cells and to determine the impact of F.nucleatum on survival in gastric cancer.METHODS Coculture of F.nucleatum with a gastric cancer cell line was performed,and changes in gene expression were investigated.Genes with significant changes in expression were identified by RNA sequencing.Pathway analysis was carried out to determine deregulated cellular functions.A cohort of gastric cancer patients undergoing gastrectomy was recruited,and nested polymerase chain reaction was performed to detect the presence of F.nucleatum in resected cancer tissues.Statistical analysis was performed to determine whether F.nucleatum colonization affects patient survival.RESULTS RNA sequencing and subsequent pathway analysis revealed a drastic interferon response induced by a high colonization load.This response peaked within 24 h and subsided after 72 h of incubation.In contrast,deregulation of actin and its regulators was observed during prolonged incubation under a low colonization load,likely altering the mobility of gastric cancer cells.According to the clinical specimen analysis,approximately one-third of the gastric cancer patients were positive for F.nucleatum,and statistical analysis indicated that the risk for colonization increases in late-stage cancer patients.Survival analysis demonstrated that F.nucleatum colonization was associated with poorer outcomes among patients also positive for Helicobacter pylori(H.pylori).CONCLUSION F.nucleatum colonization leads to deregulation of actin dynamics and likely changes cancer cell mobility.Cohort analysis demonstrated that F.nucleatum colonization leads to poorer prognosis in H.pylori-positive patients with late-stage gastric cancer.Hence,combined colonization of F.nucleatum and H.pylori is a predictive biomarker for poorer survival in late-stage gastric cancer patients treated with gastrectomy.

Impact of Fusobacterium nucleatum in the gastrointestinal tract on natural killer cells

BACKGROUND Gut microbial dysbiosis contributes to the development and progression of colorectal cancer(CRC).Natural killer(NK)cells are involved in early defense mechanisms to kill infective pathogens and tumor cells by releasing chemokines and cytokines.To better understand the relationship between the gut microbiome and CRC,it was hypothesized here that a high abundance of Fusobacterium nucleatum(F.nucleatum)in the gastrointestinal tract could cause reduced NK cell activity.AIM To identify associations between gastrointestinal tract F.nucleatum levels and NK cell activity.METHODS In vitro experiments were performed on NK cells treated with F.nucleatum,Peptostreptococcus anaerobius,and Parvimonas micra to identify the effects of gut microbiome species on NK cells.Following 24 and 48 h of treatment,NK cell counts were measured.In parallel studies,C57BL/6 mice were given broadspectrum antibiotics in their drinking water to reduce resident gut flora.After 3 wk,the mice received the various bacterial species or phosphate-buffered saline(PBS)via oral gavage every 2 d for 6 wk.At the study end,blood samples were acquired to perform NK cell activity assessment and cytokine analysis.Intestinal tissues were collected and analyzed via immunohistochemistry(IHC).RESULTS The data show that after 3 wk of broad-spectrum antibiotic treatment,levels of total bacteria and F.nucleatum were markedly decreased in mice.Gavage of F.nucleatum significantly decreased NK cell activity relative to the activities of cells from mice treated with antibiotics only and PBS.The administration of F.nucleatum decreased the proportion of NK46+cells based on IHC staining and increased the production of interleukin-1βand tumor necrosis factor-α.CONCLUSION High levels of F.nucleatum in the gastrointestinal tract reduced NK cell activity in mice,and the decrease in NK cell activity might be affected by increased proinflammatory cytokines after F.nucleatum treatment.

Salivary Fusobacterium nucleatum serves as a potential diagnostic biomarker for gastric cancer

BACKGROUND As one of the most common tumors,gastric cancer(GC)has a high mortality rate,since current examination approaches cannot achieve early diagnosis.Fusobacterium nucleatum(Fn)primarily colonized in the oral cavity,has been reported to be involved in the development of gastrointestinal tumor.Until now,little is known about the relationship between salivary Fn and GC.AIM To determine whether salivary Fn could be a biomarker to diagnose GC and explore the influence of Fn on GC cells.METHODS The abundance of Fn in saliva was quantified by droplet digital polymerase chain reaction in 120 GC patients,31 atrophic gastritis(AG)patients,35 non-AG(NAG)patients,26 gastric polyp(GP)patients,and 20 normal controls(NC)from Qilu Hospital of Shandong University from January 2019 to December 2020.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the diagnostic value of Fn as well as traditional serum tumor markers,including carcinoembryonic antigen(CEA),carbohydrate antigen(CA)19-9,and CA72-4.Transwell assay and wound-healing assay were conducted to assess the influence of Fn infection on GC cells.The expression of epithelial-mesenchymal transition(EMT)markers was detected using western blot assay.RESULTS We found that the level of salivary Fn in GC patients was significantly increased compared with those in AG,NAG,and GP patients and NC(P<0.001).ROC curve analysis showed a favorable capability of Fn(73.33% sensitivity;82.14%specificity;area under the curve:0.813)in GC diagnosis,which was superior to that of CEA,CA19-9,CA72-4,ferritin,and sialic acid.The Fn level in saliva of GC patients was increased as the TNM stage increased.GC patients with lymph node metastasis had higher Fn levels than those without metastasis.Both transwell and wound-healing assays indicated that Fn infection promoted the migration and invasion of GC cells.Western blot analysis showed that Fn infection decreased the expression of E-cadherin and increased the expressions of N-cadherin,vimentin,and snail.CONCLUSION Fn abundance in saliva could be used as a promising biomarker to diagnose GC,and Fn infection could promote GC metastasis by accelerating the EMT process.

Characterization of Fusobacterium nucleatum ATCC 23726 adhesins involved in strain-specific attachment to Porphyromonas gingivalis

Bacterial adherence is an essential virulence factor in pathogenesis and infection. Fusobacterium nucleatum has a central role in oral biofilm architecture by acting as a bridge between early Gram-positive and late Gram-negative colonizers that do not otherwise adhere to each other. In this study, we survey a key adherence interaction of F. nucleatum with Porphyromonas gingivalis, and present evidence that multiple fusobacterial adhesins have a role in the attachment of F. nucleatum ATCC 23726 to P. gingivalis in a highly strain-dependent manner. Interaction between these species displayed varying sensitivities to arginine, galactose and lactose. Arginine was found to hamper coaggregation by at least 62% and up to 89% with several P. gingivalis strains and galactose inhibition ranged from no inhibition up to 58% with the same P. gingivalis strains. Lactose consistently inhibited F. nucleatum interaction with these P. gingivalis strains ranging from 40% to 56% decrease in coaggregation. Among the adhesins involved are the previously described Fap2 and surprisingly, RadD, which was described in an earlier study for its function in attachment of F. nucleatum to Gram-positive species. We also provide evidence for the presence of at least one additional adhesin that is sensitive to arginine but unlike Fap2 and RadD, is not a member of the autotransporter family type of fusobacterial large outer membrane proteins. The strain-specific binding profile of multiple fusobacterial adhesins to P. gingivalis highlights the heterogeneity and complexity of interspecies interactions in the oral cavity.

Fusobacterium nucleatum promotes colon cancer progression by changing the mucosal microbiota and colon transcriptome in a mouse model

BACKGROUND Fusobacterium nucleatum(F.nucleatum)has long been known to cause opportunistic infections and has recently been implicated in colorectal cancer(CRC),which has attracted broad attention.However,the mechanism by which it is involved in CRC development is not fully understood.AIM To explore its potential causative role in CRC development,we evaluated the colon pathology,mucosa barrier,colon microbiota and host transcriptome profile after F.nucleatum infection in an azoxymethane/dextran sulfate sodium salt(AOM/DSS)mouse model.METHODS Three groups of mice were compared to reveal the differences,i.e.,the control,AOM/DSS-induced CRC and AOM/DSS-FUSO infection groups.RESULTS Both the AOM/DSS and AOM/DSS-FUSO groups exhibited a significantly reduced body weight and increased tumor numbers than the control group,and AOM/DSS mice with F.nucleatum infection showed the highest tumor formation ratio among the three groups.Moreover,the colon pathology was the most serious in the AOM/DSS-FUSO group.We found that the structure of the colon microbiota changed considerably after F.nucleatum infection;striking differences in mucosal microbial population patterns were observed between the AOM/DSS-FUSO and AOM/DSS groups,and inflammation-inducing bacteria were enriched in the mucosal microbiota in the AOM/DSS-FUSO group.By comparing intestinal transcriptomics data from AOM vs AOM/DSSFUSO mice,we showed that transcriptional activity was strongly affected by dysbiosis of the gut microbiota.The most microbiota-sensitive genes were oncogenes in the intestine,and the cyclic adenosine monophosphate signaling pathway,neuroactive ligand–receptor interaction,PPAR signaling pathway,retinol metabolism,mineral absorption and drug metabolism were highly enriched in the AOM/DSS-FUSO group.Additionally,we showed that microbial dysbiosis driven by F.nucleatum infection enriched eight taxa belonging to Proteobacteria,which correlates with increased expression of oncogenic genes.CONCLUSION Our study demonstrated that F.nucleatum infection altered the colon mucosal microbiota by enriching pathogens related to the development of CRC,providing new insights into the role of F.nucleatum in the oncogenic microbial environment of the colon.

Fusobacterium nucleatum——The Cause of Human Colorectal Cancer

Objective: Accumulating evidence indicates that the gut microbiome has an increasingly important role in human disease and health. Fusobacterium nucleatum has been identified in several studies as the leading gut bacterium which is present in colorectal cancer (CRC). Still it is not clear if Fusobacterium plays a causal role. Methods: To explore the cause-effect relationship between Fusobacterium nucleatum and colorectal cancer, a systematic review and re-analysis of studies published were performed. The method of the conditio sine qua non relationship was used to proof the hypothesis without Fusobacterium nucleatum infection, no colorectal cancer. The mathematical formula of the causal relationship k was used to proof the hypothesis, whether there is a cause-effect relationship between Fusobacterium nucleatum and colorectal cancer. Significance was indicated by a p-value of less than 0.05. Result: The data analyzed support the Null-hypothesis that without Fusobacterium nucleatum infection, no colorectal cancer. In the same respect, the studies analyzed provide highly significant cause-effect relationship between Fusobacterium nucleatum and colorectal cancer. Conclusion: The findings of this study suggest that Fusobacterium (nucleatum) is the cause of colorectal cancer.

Fusobacterium Nucleatum Is a Risk Factor for Metastatic Colorectal Cancer

Objective Increasing evidence has indicated that there is a correlation between Fusobacterium nucleatum(F.nucleatum)abundance and poor prognosis of colorectal cancer(CRC).Furthermore,tumor metastasis plays a decisive role in the prognosis of CRC patients.Therefore,it was hypothesized that the abundance of F.nucleatum in CRC tissues affects the tumor metastasis.Methods In the present study,F.nucleatum DNA obtained from 141 resected CRC samples was quantified by qPCR to determine whether there were differences in F.nucleatum abundance between groups with and without CRC metastasis.Results The results revealed that F.nucleatum was more abundant in CRC patients with metastasis,and CRC tissues enriched with F.nucleatum had a higher risk of lymph node metastasis and distant metastasis.The receiver operating characteristic curve indicated that F.nucleatum in CRC tissues could be used as an indicator for CRC metastasis,to some extent.Furthermore,the in vitro experiments(electron microscopy,and migration and invasion trials)revealed that F.nucleatum was a highly invasive bacterial strain,and could significantly enhance the invasion and migration capacity of SW480 and SW620 cells.In addition,a meta-analysis comprehensively indicated a slight correlation between F.nucleatum abundance and advanced CRC stage(RR=1.17,95%CI:1.00–1.37,P=0.04,random effect).Conclusion There is a correlation between F.nucleatum abundance and CRC metastasis,and F.nucleatum may serve as a metastasis biomarker for CRC patients.

Infected Iliac Artery Aneurysm Concomitant with Liver Abscess Caused by Fusobacterium nucleatum

We report a case of infected iliac artery aneurysm concomitant with liver abscesses caused by Fusobacterium nucleatum. A 58-year-old man developed an aneurysm of the right common iliac artery and liver abscesses. The aneurysm was resected and a femoro-femoral crossover bypass with a knitted Dacron graft was performed for impending rupture. Anaerobic cultures obtained from blood and intramural thrombus were positive for Fusobacterium nucleatum. With antibiotics, the liver abscesses disappeared without drainage. Iliopsoas abscesses developed after surgery, but it was controlled with antibiotics. The patient was free of infection 1 year after the surgery. The causative bacterium was suspected to originate in the oral cavity, because the patient had a notable history of poor chronic periodontal conditions. Clinically, infected aortoiliac aneurysm complicated by Fusobacterium is extremely rare relative to the prevalence of the pathogenic bacterium. However, it is noteworthy that Fusobacterium can cause this condition.

Complicated Fusobacterium necrophorum mastoiditis–More than meets the eye

Otitis media is common in children and Fusobacterium species are an emerging causative pathogen.These species have virulence factors which increase the risk of complicated otitis media.We discuss a case of F.necrophorum infection resulting in significant intracranial disease to highlight the epidemiology of these infections,risk factors for complicated disease and signs and symptoms to guide diagnosis and investigation.