About a Possible Impact of Endodontic Infections by Fusobacterium nucleatum or Porphyromonas gingivalis on Oral Carcinogenesis: A Literature Overview.

Periodontitis is linked to the onset and progression of oral squamous cell carcinoma (OSCC), an epidemiologically frequent and clinically aggressive malignancy. In this context, Fusobacterium (F.) nucleatum and Porphyromonas (P.) gingivalis, two bacteria that cause periodontitis, are found in OSCC tissues as well as in oral premalignant lesions, where they exert pro-tumorigenic activities. Since the two bacteria are present also in endodontic diseases, playing a role in their pathogenesis, here we analyze the literature searching for information on the impact that endodontic infection by P. gingivalis or F. nucleatum could have on cellular and molecular events involved in oral carcinogenesis. Results from the reviewed papers indicate that infection by P. gingivalis and/or F. nucleatum triggers the production of inflammatory cytokines and growth factors in dental pulp cells or periodontal cells, affecting the survival, proliferation, invasion, and differentiation of OSCC cells. In addition, the two bacteria and the cytokines they induce halt the differentiation and stimulate the proliferation and invasion of stem cells populating the dental pulp or the periodontium. Although most of the literature confutes the possibility that bacteria-induced endodontic inflammatory diseases could impact on oral carcinogenesis, the papers we have analyzed and discussed herein recommend further investigations on this topic.

The Clinical Value of Cranial CT Venography for Predicting Fusobacterium necrophorum as the Causative Agent in Children with Complicated Acute Mastoiditis.

BACKGROUND AND PURPOSE: Fusobacterium necrophorum (F necrophorum) is an anaerobic bacteria that causes invasive head and neck infections in children. Several studies have demonstrated an increasing prevalence of F necrophorum as the causative agent in acute mastoiditis in children, with associated high rates of intracranial complications such as epidural abscess and sinus venous thrombosis, to name a few. F necrophorum requires a treatment protocol that differs from the empiric treatment that is tailored to more common pathogens (eg, group A streptococci, Streptococcus pneumonia), and hence expediting the diagnosis is important. For evaluating complicated acute mastoiditis in children, cranial CT venography remains the imaging study of choice in most medical centers due to its availability in emergency situations. Based on our clinical experience, our hypothesis is that children with F necrophorum-associated complicated acute mastoiditis can be differentiated from those with other etiologies using CT venography. MATERIALS AND METHODS: CT venography studies of 76 children hospitalized and treated for complicated acute mastoiditis were retrospectively reviewed. Retrieved imaging data included intracranial complications (epidural abscess, sinus venous thrombosis), cranial bone-related complications, and extracranial complications (subperiosteal abscess, temporomandibular joint abscess, and soft-tissue inflammation). The cohort was divided into children with F necrophorum-related disease (study group) and those with non-F necrophorum-related disease (control group). RESULTS: Thirty-seven children (49%) comprised the study group, and 39 children in whom the causative agents were other bacteria comprised the control group. There were significantly higher rates of complications in the study group: sinus venous thrombosis (P < .001), perisigmoid epidural abscess (P = .036), and extramastoid osteomyelitis (P < .001). Thrombosis in venous sites beyond the sigmoid sinus and jugular foramen (a pattern consistent with an otogenic variant of Lemierre syndrome) and emphysematous osteomyelitis were found only among children in the F necrophorum-related study group (32% and 22% accordingly). CONCLUSIONS: In children with complicated acute mastoiditis, CT venography findings of emphysematous osteomyelitis and/or thrombosis in venous sites beyond the sigmoid sinus and jugular foramen (a pattern consistent with the otogenic variant of Lemierre syndrome) should lead the radiologist to suggest F necrophorum-related mastoiditis.

Fusobacterium nucleatum: An Overview of Evidence, Demi-Decadal Trends, and Its Role in Adverse Pregnancy Outcomes and Various Gynecological Diseases, including Cancers.

Gynecological and obstetric infectious diseases are crucial to women's health. There is growing evidence that links the presence of Fusobacterium nucleatum (F. nucleatum), an anaerobic oral commensal and potential periodontal pathogen, to the development and progression of various human diseases, including cancers. While the role of this opportunistic oral pathogen has been extensively studied in colorectal cancer in recent years, research on its epidemiological evidence and mechanistic link to gynecological diseases (GDs) is still ongoing. Thus, the present review, which is the first of its kind, aims to undertake a comprehensive and critical reappraisal of F. nucleatum, including the genetics and mechanistic role in promoting adverse pregnancy outcomes (APOs) and various GDs, including cancers. Additionally, this review discusses new conceptual advances that link the immunomodulatory role of F. nucleatum to the development and progression of breast, ovarian, endometrial, and cervical carcinomas through the activation of various direct and indirect signaling pathways. However, further studies are needed to explore and elucidate the highly dynamic process of host-F. nucleatum interactions and discover new pathways, which will pave the way for the development of better preventive and therapeutic strategies against this pathobiont.

Lemierre syndrome with pulmonary empyema caused by Prevotella intermedia.

Lemierre syndrome is a rare disease that is most often caused by Fusobacterium necrophorum We present a case caused by Prevotella intermedia in a young, healthy man, complicated by multiple cavitary lung lesions, loculated pleural effusions requiring chest tube placement and trapezius abscess. Our case highlights (a) P. intermedia as a rare cause of Lemierre syndrome and (b) clinical response to appropriate antimicrobial therapy may be protracted.

Fusobacterium necrophorum intratonsillar abscess as a source of bacteremia in a patient with a history of substance abuse.

A 22-year-old male, with a history of recreational drug use, was admitted with a 24-hour history of sore throat, bilateral otalgia, fever, chills, sweats, and pain in the upper chest. The blood cultures were positive for Fusobacterium necrophorum. A thoracic and neck soft tissue computed tomography (CT) scan revealed an intratonsillar abscess and pulmonary septic emboli. Initial treatment with Piperacillin-tazobactam and Clindamycin was de-escalated after 5 days. The patient made a complete recovery after 22 days of antibiotic treatment.

Fusobacterium nucleatum bacteremia complicated with intracranial Porphyromonas gingivalis and HSV-1 infection: a case report and literature review.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) belongs to the genus Fusobacterium, which is a gram-negative obligate anaerobic bacterium. Bacteremia associated with F. nucleatum is a serious complication, which is not common in clinic, especially when it is combined with other intracranial pathogenic microorganism infection. We reported for the first time a case of F. nucleatum bacteremia combined with intracranial Porphyromonas gingivalis (P. gingivalis) and herpes simplex virus type 1(HSV-1) infection. CASE PRESENTATION: A 60-year-old woman was admitted to our hospital with a headache for a week that worsened for 2 days. Combined with history, physical signs and examination, it was characterized as ischemic cerebrovascular disease (ICVD). F. nucleatum was detected in blood by matrix-assisted laser desorption/ionization time-offight mass spectrometry (MALDI-TOF-MS). Meanwhile, P. gingivalis and HSV-1 in cerebrospinal fluid (CSF) were identified by metagenome next generation sequencing (mNGS). After a quick diagnosis and a combination of antibiotics and antiviral treatment, the patient recovered and was discharged. CONCLUSION: To our knowledge, this is the first report of intracranial P. gingivalis and HSV-1 infection combined with F. nucleatum bacteremia.

Fusobacterium/Peptostreptococcus - A Case Report of Community- Acquired Empyema Resulting in Surgical Decortication with Prolonged Antibiotic Therapy: A Case Series and Review of the Literature.

Background: Infections caused by anaerobic bacteria occur frequently and can be serious and life-threatening. Anaerobes are a rare cause of community-acquired pneumonia with Streptococcus pneumonia and respiratory viruses being the most frequently detected pathogens. We, herein, report a case of Fusobacterium/Peptostreptococcus parapneumonic effusion with empyema in a patient without risk factors for aspiration pneumonia. This case presents an opportunity to discuss an unusual case of community-acquired empyema secondary to anaerobic infection in a patient without the common risk factors for aspiration.

Case Presentation: A 59-year-old male patient without significant past medical history apart from a twenty-five-year history of smoking presented due to left flank pain and shortness of breath. Findings of a complicated parapneumonic effusion were found on imaging, resulting in surgical decortication and prolonged antibiotic therapy.

Discussion: Parapneumonic effusions and empyema are relatively common complications of pneumonia. It is important to note that the incidence of anaerobic empyema has been on the rise due to more modern culturing techniques.

Conclusion: This case highlights an unusual presentation of community-acquired empyema secondary to anaerobes without any risk factors for aspiration pneumonia. Therefore, clinicians should consider the possibility of anaerobic coverage in the treatment of community-acquired empyema in the appropriate setting.

Lemierre syndrome: a diagnostic dilemma of critical care in the post-COVID era.

Lemierre syndrome (LS) is referred to as the 'forgotten Disease' owing to its rarity in the postantibiotic era with an estimated yearly incidence of 1/million population. The classic triad of LS includes internal jugular vein thrombosis, oropharyngeal infection and metastatic septic emboli. We present a case of typical LS with Fusobacterium and Prevotella infection, presenting with peritonsillar abscess and jugular vein thrombosis complicated by sepsis, acute hypoxic respiratory failure due to multiple pulmonary emboli and severe thrombocytopaenia in the absence of disseminated intravascular coagulation.

Fabrication of hyaluronic acid-inulin coated Enterococcus faecium for colon-targeted delivery to fight Fusobacterium nucleatum.

The abundance of Fusobacterium nucleatum (F. nucleatum) is highly associated with the development and poor prognosis of colorectal cancer (CRC), which is regarded as a promising target for CRC. However, until now, the novel strategy to clear F. nucleatum in the colon and CRC has not been well proposed. Herein, a probiotic strain Enterococcus faecium (E. faecium, EF47) is verified to secrete various organic acids and bacteriocins to exert superior antimicrobial activity towards F. nucleatum. However, the oral delivery of EF47 is affected by the complex digestive tract environment, so we design the hyaluronic acid-inulin (HA-IN) coated EF47 for colon-targeted delivery to fight F. nucleatum. IN can protect EF47 from the harsh gastrointestinal tract environment and is degraded specifically in the colon, acting as prebiotics to further promote the proliferation of EF47. The exposed HA can also enhance the targeting effect to the tumor area via the interaction with the CD44 receptor on the tumor cells, which is confirmed to increase the adhesive ability in tumor tissues and inhibit the growth of F. nucleatum. Therefore, this colon-targeted delivery system provides a novel platform to realize high-activity and adhesive delivery of probiotics to assist the therapeutic efficiency of CRC.

Effects of metronidazole on colorectal cancer occurrence and colorectal cancer liver metastases by regulating Fusobacterium nucleatum in mice.

OBJECTIVE: Colorectal cancer (CRC) represents a leading cause of cancer-related deaths. Metronidazole (MNZ) is exceedingly implicated in CRC. This study explored the roles of MNZ in mouse CRC occurrence and liver metastasis (CRLM). METHODS: Male BALB/c nude mice were subjected to CRC and CRLM modeling, orally administration with MNZ (1 g/L) 1 week before modeling, and disease activity index (DAI) evaluation. Fresh stool and anal swab samples were collected on the morning of the 28th day after modeling. The relative expression of Fusobacterium nucleatum (F. nucleatum) DNA was assessed by quantitative polymerase chain reaction. After euthanasia, tumor tissues and liver tissues were separated and the tumor volume and weight change were measured. The liver tissues were stained with hematoxylin-eosin to quantitatively analyze the metastatic liver nodules. Malignant tumor biomarker Ki67 protein levels in liver tissues/DNA from stool samples were detected by immunohistochemistry/high-throughput 16S rRNA gene sequencing. Bioinformatics analysis was performed on the raw sequence data to analyze microbial community richness (Chao1 index, ACE index) and microbial community diversity (Shannon index). RESULTS: The DAI and F. nucleatum DNA relative expression in feces and anal swabs of the CRC and CRLM groups were raised and repressed after MNZ intervention. MNZ repressed tumor occurrence and growth in mice to a certain extent, alleviated CRLM malignant degree (reduced liver metastases and Ki67-positive cell density/number), and suppressed CRC liver metastasis by regulating intestinal flora structure, which affected the intestinal characteristic flora of CRC and CRLM mice. CONCLUSION: MNZ suppressed CRC occurrence and CRLM in mice by regulating intestinal F. nucleatum.

Fusobacterium Necrophorum bacteremia involving multi-organ systems.

A 62-year-old African American man with a history of avascular necrosis (AVN) of the right hip joint presented with severe right hip pain, dyspnea, fever, tachycardia, and hypertension. Computed tomography (CT) scan showed bilateral airspace opacities with a mild tree-in-bud nodularity in the left lower lobe. Ultrasonography of the lower extremities revealed a deep venous thrombus (DVT) in the right deep veins. Blood cultures grew Fusobacterium necrophorum. CT and magnetic resonance imaging showed right hip joint destruction and septic arthritis. The patient had a complicated hospital course leading to total hip arthroplasty with antibiotic-impregnated cementing.

Fusobacterium nucleatum upregulates MMP7 to promote metastasis-related characteristics of colorectal cancer cell via activating MAPK(JNK)-AP1 axis.

BACKGROUND: Colorectal cancer (CRC) is the third most common malignant tumor. Fusobacterium nucleatum (F. nucleatum) is overabundant in CRC and associated with metastasis, but the role of F. nucleatum in CRC cell migration and metastasis has not been fully elucidated. METHODS: Differential gene analysis, protein-protein interaction, robust rank aggregation analysis, functional enrichment analysis, and gene set variation analysis were used to figure out the potential vital genes and biological functions affected by F. nucleatum infection. The 16S rDNA sequencing and q-PCR were used to detect the abundance of F. nucleatum in tissues and stools. Then, we assessed the effect of F. nucleatum on CRC cell migration by wound healing and transwell assays, and confirmed the role of Matrix metalloproteinase 7 (MMP7) induced by F. nucleatum in cell migration. Furthermore, we dissected the mechanisms involved in F. nucleatum induced MMP7 expression. We also investigated the MMP7 expression in clinical samples and its correlation with prognosis in CRC patients. Finally, we screened out potential small molecular drugs that targeted MMP7 using the HERB database and molecular docking. RESULTS: F. nucleatum infection altered the gene expression profile and affected immune response, inflammation, biosynthesis, metabolism, adhesion and motility related biological functions in CRC. F. nucleatum was enriched in CRC and promoted the migration of CRC cell by upregulating MMP7 in vitro. MMP7 expression induced by F. nucleatum infection was mediated by the MAPK(JNK)-AP1 axis. MMP7 was highly expressed in CRC and correlated with CMS4 and poor clinical prognosis. Small molecular drugs such as δ-tocotrienol, 3,4-benzopyrene, tea polyphenols, and gallic catechin served as potential targeted therapeutic drugs for F. nucleatum induced MMP7 in CRC. CONCLUSIONS: Our study showed that F. nucleatum promoted metastasis-related characteristics of CRC cell by upregulating MMP7 via MAPK(JNK)-AP1 axis. F. nucleatum and MMP7 may serve as potential therapeutic targets for repressing CRC advance and metastasis.

Delivery of short chain fatty acid butyrate to overcome Fusobacterium nucleatum-induced chemoresistance.

The gut microbiota is closely associated with the progression of colorectal cancer (CRC) in which Fusobacterium nucleatum (F. nucleatum) was found to induce cancer resistance to chemotherapeutics. To relieve F. nucleatum-induced drug resistance, herein, we found that short-chain fatty acid butyrate can inhibit the growth, enrichment and adhesion of F. nucleatum in colorectal cancer tissues by downregulating the expression of adhesion-associated outer membrane proteins, including RadD, FomA, and FadA, to reduce the colonization and invasion of F. nucleatum and relieve the chemoresistance induced by F. nucleatum. Leveraging the killing effect of butyrate on F. nucleatum, sodium butyrate (NaBu) was encapsulated in liposomes or prepared as NaBu tablets with Eudragit S100 coating and administered by intravenous injection or oral administration, respectively. Interestingly, both intravenous administration of NaBu liposomes and oral delivery of NaBu tablets could effectively inhibit the proliferation of F. nucleatum and significantly improve the therapeutic efficacy of oxaliplatin in mice with subcutaneous colorectal tumors, orthotopic colorectal tumors and even spontaneously formed colorectal tumors. Thus, our work provides a simple but effective formulation of NaBu to relieve F. nucleatum-induced chemoresistance, exhibiting ideal clinical application prospects.

Complex Lemierre syndrome with multisystemic abscesses.

We present here the challenging case of severe Lemierre syndrome in a healthy woman in her late twenties, whose clinical presentation was characterised by lung abscesses and disseminated systemic abscesses in the brain, the abdomen and the soft-tissues, as a likely consequence of a patent foramen ovale. Blood cultures were positive for Fusobacterium necrophorum and a right lingual vein thrombosis was detected at a late stage when the patient developed a septic shock. Initial antimicrobial therapy with metronidazole and ceftriaxone was modified to meropenem due to progressive worsening. The patient underwent laparoscopy and neurosurgical drainage of a cerebral abscess. She spent many days in the intensive care unit and recovered fully after 6 weeks on meropenem therapy. Although considered rare, the incidence of Lemierre syndrome, a potentially life-threatening condition, is increasing. The clinician should promptly recognise and treat it while being aware of its potential atypical presentations.

Fusobacterium nucleatum stimulates cell proliferation and promotes PD-L1 expression via IFIT1-related signal in colorectal cancer.

Fusobacterium nucleatum (F. nucleatum) is enriched in colorectal cancer (CRC) tissues and a high amount of F. nucleatum was associated with an immunosuppressive tumor environment. PD-L1 is an important immune checkpoint expressed on tumor cells and promotes tumor immune escape. Whether PD-L1 is regulated by F. nucleatum is still unclear. We demonstrated that F. nucleatum promoted CRC progression and upregulated PD-L1 protein expression in CRC cell lines. Combined m6A-seq and RNA-seq identified m6A-modified IFIT1 mediating F. nucleatum induced PD-L1 upregulation. IFIT1 mRNA was modified with m6A modifications in 3'UTR and the m6A levels were altered by F. nucleatum treatment. Our results also indicated that IFIT1 served as a potential oncogene in CRC and regulated PD-L1 protein levels through altering PD-L1 ubiquitination. Clinical CRC data confirmed the correlation among F. nucleatum abundance, IFIT1 and PD-L1 expressions. Our work highlighted the function of F. nucleatum in stimulating PD-L1 expression through m6A-modified IFIT1 and provided new aspects for understanding F. nucleatum mediated immune escape.

Atypical involvement of the thyro-linguo-facial vein in Lemierre syndrome.

Fusobacterium necrophorum is a Gram-negative anaerobic bacterium that can lead to severe infection in young patients even without immunodeficiency. Due to the length of time for isolation and speciation of this Gram-negative bacillus (typically 5-8 days), and its potential mortality, broad-spectrum antibiotic therapy should be started without delay. With a cervical thrombosis, even on an unusual site and with a standard condition such as tonsillitis, Lemierre syndrome should be considered. We report a case of Lemierre syndrome in a previously healthy young woman.

Fusobacterium and Colorectal Cancer: Important Association or Random Coincidence?

The role of the microbiome in human cancer has become an area of intensive research and controversy. Many reports have highlighted the physical association of Fusobacterium with colorectal cancer. This association has provided diagnostic and therapeutic promise but has also given rise to several controversies regarding the influence of Fusobacterium species on human colorectal cancer. Here, we discuss two areas of controversy surrounding this emerging pathogen: the influence of Fusobacterium on colorectal cancer proliferation and the effect of Fusobacterium on the immune microenvironment of colorectal cancer.

Myometritis with pelvic septic vein thrombophlebitis secondary to Fusobacterium necrophorum sepsis.

A young woman in her 20s presented with fever, abdominal pain and malodourous vaginal discharge. She was found to be in septic shock, in the setting of a recent medical abortion with subsequent intrauterine device placement. Her blood cultures grew Fusobacterium necrophorum Despite appropriate antibiotic therapy, the fever failed to defervesce. Subsequent evaluation revealed septic thrombophlebitis of the right gonadal vein and branches of the right iliac vein. She improved with a prolonged course of targeted antimicrobial therapy.