RESUMO
Fusobacterium nucleatum (Fn), a bacterium present in the human oral cavity and rarely found in the lower gastrointestinal tract of healthy individuals1, is enriched in human colorectal cancer (CRC) tumours2-5. High intratumoural Fn loads are associated with recurrence, metastases and poorer patient prognosis5-8. Here, to delineate Fn genetic factors facilitating tumour colonization, we generated closed genomes for 135 Fn strains; 80 oral strains from individuals without cancer and 55 unique cancer strains cultured from tumours from 51 patients with CRC. Pangenomic analyses identified 483 CRC-enriched genetic factors. Tumour-isolated strains predominantly belong to Fn subspecies animalis (Fna). However, genomic analyses reveal that Fna, considered a single subspecies, is instead composed of two distinct clades (Fna C1 and Fna C2). Of these, only Fna C2 dominates the CRC tumour niche. Inter-Fna analyses identified 195 Fna C2-associated genetic factors consistent with increased metabolic potential and colonization of the gastrointestinal tract. In support of this, Fna C2-treated mice had an increased number of intestinal adenomas and altered metabolites. Microbiome analysis of human tumour tissue from 116 patients with CRC demonstrated Fna C2 enrichment. Comparison of 62 paired specimens showed that only Fna C2 is tumour enriched compared to normal adjacent tissue. This was further supported by metagenomic analysis of stool samples from 627 patients with CRC and 619 healthy individuals. Collectively, our results identify the Fna clade bifurcation, show that specifically Fna C2 drives the reported Fn enrichment in human CRC and reveal the genetic underpinnings of pathoadaptation of Fna C2 to the CRC niche.
Assuntos
Neoplasias Colorretais , Fusobacterium nucleatum , Animais , Humanos , Camundongos , Adenoma/microbiologia , Estudos de Casos e Controles , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , Fezes/microbiologia , Fusobacterium nucleatum/classificação , Fusobacterium nucleatum/genética , Fusobacterium nucleatum/isolamento & purificação , Fusobacterium nucleatum/patogenicidade , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Genoma Bacteriano/genética , Boca/microbiologia , FemininoRESUMO
BACKGROUND: Mounting evidence suggests a significant role of the gut microbiota in the development and progression of colorectal cancer (CRC). In particular, an over-representation of oral pathogens has been linked to CRC. The aim of this study was to further investigate the faecal microbial landscape of CRC patients, with a focus on the oral pathogens Parvimonas micra and Fusobacterium nucleatum. METHODS: In this study, 16S rRNA sequencing was conducted using faecal samples from CRC patients (n = 275) and controls without pathological findings (n = 95). RESULTS: We discovered a significant difference in microbial composition depending on tumour location and microsatellite instability (MSI) status, with P. micra, F. nucleatum, and Peptostreptococcus stomatis found to be more abundant in patients with MSI tumours. Moreover, P. micra and F. nucleatum were associated with a cluster of CRC-related bacteria including Bacteroides fragilis as well as with other oral pathogens such as P. stomatis and various Porphyromonas species. This cluster was distinctly different in the control group, suggesting its potential linkage with CRC. CONCLUSIONS: Our results suggest a similar distribution of several CRC-associated bacteria within CRC patients, underscoring the importance of considering the concomitant presence of bacterial species in studies investigating the mechanisms of CRC development and progression.
Assuntos
Neoplasias Colorretais , Humanos , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Fezes/microbiologia , RNA Ribossômico 16S/genética , Boca/microbiologia , Firmicutes/isolamento & purificação , Firmicutes/genética , Fusobacterium nucleatum/isolamento & purificação , Estudos de Casos e Controles , Instabilidade de Microssatélites , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificaçãoRESUMO
We examined Fusobacterium nucreatum (F. nucleatum) and whole Fusobacterium species (Pan-fusobacterium) in non-neoplastic Barrett's esophagus (BE) from patients without cancer (n = 67; N group), with esophageal adenocarcinoma (EAC) (n = 27) and EAC tissue (n = 22). F. nucleatum was only detectable in 22.7% of EAC tissue. Pan-fusobacterium was enriched in EAC tissue and associated with aggressive clinicopathological features. Amount of Pan-fusobacterium in non-neoplastic BE was correlated with presence of hital hernia and telomere shortening. The result suggested potential association of Fusobacterium species in EAC and BE, featuring clinicpathological and molecular features.
Assuntos
Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/microbiologia , Neoplasias Esofágicas/patologia , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Esôfago de Barrett/microbiologia , Esôfago de Barrett/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Fusobacterium/isolamento & purificação , Fusobacterium/genética , Fusobacterium nucleatum/isolamento & purificação , AdultoRESUMO
Pleural empyema can lead to significant morbidity and mortality despite chest drainage and antibiotic treatment, necessitating novel and minimally invasive interventions. Fusobacterium nucleatum is an obligate anaerobe found in the human oral and gut microbiota. Advances in sequencing and puncture techniques have made it common to detect anaerobic bacteria in empyema cases. In this report, we describe the case of a 65-year-old man with hypertension who presented with a left-sided encapsulated pleural effusion. Initial fluid analysis using metagenomic next-generation sequencing (mNGS) revealed the presence of Fusobacterium nucleatum and Aspergillus chevalieri. Unfortunately, the patient experienced worsening pleural effusion despite drainage and antimicrobial therapy. Ultimately, successful treatment was achieved through intrapleural metronidazole therapy in conjunction with systemic antibiotics. The present case showed that intrapleural antibiotic therapy is a promising measure for pleural empyema.
Assuntos
Antibacterianos , Empiema Pleural , Fusobacterium nucleatum , Terapia de Salvação , Humanos , Masculino , Idoso , Empiema Pleural/tratamento farmacológico , Empiema Pleural/microbiologia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Fusobacterium nucleatum/efeitos dos fármacos , Fusobacterium nucleatum/isolamento & purificação , Fusobacterium nucleatum/genética , Infecções por Fusobacterium/tratamento farmacológico , Infecções por Fusobacterium/complicações , Infecções por Fusobacterium/microbiologia , Metronidazol/uso terapêutico , Metronidazol/administração & dosagem , Sequenciamento de Nucleotídeos em Larga Escala , Resultado do TratamentoRESUMO
OBJECTIVE: This study aims to analyse the association between the baseline microbial load of selected periodontopathogenic bacteria collected from gingival crevicular fluid (GCF) and the primary outcome of steps I and II therapy. MATERIALS AND METHODS: 222 patients with stage III periodontitis were included into this retrospective analysis that received steps 1 and 2 periodontal therapy without adjunctive systemic antibiotics. Baseline GCF samples were quantitatively analysed using ELISA-based kits for levels of periodontopathogens (Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn), Treponema denticola (Td), and Tannerella forsythia (Tf)) and associated with the primary therapy outcome using a "treat-to-target" therapy endpoint (TE) defined as ≤ 4 sites with PD ≥ 5 mm six months after therapy. RESULTS: 38.2% of the patients achieved TE. Patients failing to achieve TE revealed significantly increased levels of Pg, Fn, and Tf at baseline (Pg: p = 0.010, Fn: p = 0.008 Tf: p = 0.004). Multivariate binary logistic regression adjusted for sex, mean probing depth, diabetes, and current smoking status showed an independent relationship between Tf and the TE (aOR 2.570, p = 0.023). CONCLUSION: Increased microbial load is associated with decreased responsiveness to therapy. The findings suggest that specifically baseline Tf levels are associated with poorer treatment outcomes and might improve the accuracy of periodontal diagnosis. CLINICAL RELEVANCE: The findings of this study support the concept of a critical biomass that is sufficient to induce and maintain an immune response within the periodontal pocket, which ultimately leads to irreversible tissue destruction. However, calculating this level in advance may serve as an early indicator for intervention. KEY FINDING: Baseline Tannerella forsythia levels are associated with poorer treatment outcome.
Assuntos
Biomarcadores , Líquido do Sulco Gengival , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Líquido do Sulco Gengival/microbiologia , Líquido do Sulco Gengival/química , Resultado do Tratamento , Biomarcadores/análise , Ensaio de Imunoadsorção Enzimática , Carga Bacteriana , Adulto , Treponema denticola/isolamento & purificação , Porphyromonas gingivalis/isolamento & purificação , Fusobacterium nucleatum/isolamento & purificação , Tannerella forsythia/isolamento & purificação , Periodontite/microbiologia , Periodontite/terapia , Aggregatibacter actinomycetemcomitans/isolamento & purificação , Prevotella intermedia/isolamento & purificaçãoRESUMO
BACKGROUND: Colorectal cancer (CRC) is a significant global health concern, and understanding the role of specific bacterial infections in its development and progression is of increasing interest. This cross-sectional study investigated the associations between Bacteroides fragilis (B. fragilis) and Fusobacterium nucleatum (F. nucleatum) infections and Vietnamese CRC patients. METHODS: 192 patients with either polyps or CRC at varying stages were recruited from May 2017 to December 2020. Real-time PCR assessed infection rates and bacterial loads in CRC tissues. RESULTS: B. fragilis infection was notably higher in CRC tissues (51.6 %) than polyps (9.4 %), with a fivefold higher relative load. Positive associations were found in stages II and III, indicating a fivefold increase in CRC progression risk. F. nucleatum infection rates were significantly higher in CRC tissues (55.2 %) than in polyps (10.5 %). In stage II, the infection rate exceeded that in adjacent tissues. The relative load of F. nucleatum was higher in stage III than in stages I and II. Positive F. nucleatum patients had a 3.2 times higher risk of CRC progression. CONCLUSION: These findings suggest associations between loading of F. nucleatum or/and B. fragilis with the advanced stages of CRC.
Assuntos
Infecções por Bacteroides , Bacteroides fragilis , Neoplasias Colorretais , Infecções por Fusobacterium , Fusobacterium nucleatum , Humanos , Neoplasias Colorretais/microbiologia , Bacteroides fragilis/isolamento & purificação , Bacteroides fragilis/genética , Fusobacterium nucleatum/isolamento & purificação , Infecções por Fusobacterium/microbiologia , Infecções por Fusobacterium/epidemiologia , Infecções por Fusobacterium/complicações , Masculino , Feminino , Vietnã/epidemiologia , Pessoa de Meia-Idade , Estudos Transversais , Infecções por Bacteroides/microbiologia , Infecções por Bacteroides/epidemiologia , Idoso , Adulto , Carga Bacteriana , População do Sudeste AsiáticoRESUMO
Intestinal dysbiosis is a major contributor to colorectal cancer (CRC) development, leading to bacterial translocation into the bloodstream. This study aimed to evaluate the presence of circulated bacterial DNA (cbDNA) in CRC patients (n = 75) and healthy individuals (n = 25). DNA extracted from peripheral blood was analyzed using PCR, with specific primers targeting 16S rRNA, Escherichia coli (E. coli), and Fusobacterium nucleatum (F. nucleatum). High 16S rRNA and E. coli detections were observed in all patients and controls. Only the detection of F. nucleatum was significantly higher in metastatic non-excised CRC, compared to controls (p < 0.001), non-metastatic excised CRC (p = 0.023), and metastatic excised CRC (p = 0.023). This effect was mainly attributed to the presence of the primary tumor (p = 0.006) but not the presence of distant metastases (p = 0.217). The association of cbDNA with other clinical parameters or co-morbidities was also evaluated, revealing a higher detection of E. coli in CRC patients with diabetes (p = 0.004). These results highlighted the importance of bacterial translocation in CRC patients and the potential role of F. nucleatum as an intratumoral oncomicrobe in CRC.
Assuntos
Neoplasias Colorretais , DNA Bacteriano , Escherichia coli , Fusobacterium nucleatum , RNA Ribossômico 16S , Humanos , Fusobacterium nucleatum/genética , Fusobacterium nucleatum/isolamento & purificação , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Masculino , Feminino , Pessoa de Meia-Idade , DNA Bacteriano/genética , DNA Bacteriano/sangue , Idoso , Escherichia coli/genética , RNA Ribossômico 16S/genética , Disbiose/microbiologia , Adulto , Estudos de Casos e Controles , Translocação Bacteriana , Idoso de 80 Anos ou mais , Infecções por Fusobacterium/microbiologia , Infecções por Fusobacterium/sangue , Infecções por Fusobacterium/complicaçõesRESUMO
BACKGROUND: Crohn's disease (CD)-associated periodontitis is common. However, the role of periodontal pathogens in the Coexistence of CD and periodontal disease remains unclear. METHODS: To investigate the potential relationship mediated by periodontal pathogens between periodontitis and CD, we collected salivary samples from healthy participants (H group, n = 12), patients with CD (Ch group, n = 10), patients with periodontitis (Ps group, n = 12), and patients with Coexistence of CD and periodontal disease (Cp group, n = 12) and analyzed them by 16 S rRNA sequencing. RESULTS: Patients with Coexistence of CD and periodontal disease had increased levels of Fusobacterium, Actinomyces, Leptotrichia, and Prevotella, which correlated with the severity of periodontitis. Conversely, the levels of Streptococcus, Neisseria, Haemophilus, and Gemella, which decreased in Coexistence of CD and periodontal disease, were negatively correlated with the severity of periodontitis. To further investigate the role of periodontal pathogens in CD development, representative periodontal pathogens causing periodontitis, Porphyromonas gingivalis and Fusobacterium nucleatum, were administered to mice. These pathogens migrate to, and colonize, the gut, accelerating CD progression and aggravating colitis, and even systemic inflammation. In vitro experiments using a Caco-2/periodontal pathogen coculture revealed that P. gingivalis and F. nucleatum increased intestinal permeability by directly disrupting the tight junctions of intestinal epithelial cells. CONCLUSION: Our findings strongly suggest that periodontal pathogens play a role in the relationship between periodontitis and CD. These results provide a basis for understanding the pathogenesis of Coexistence of CD and periodontal disease and may lead to the development of novel therapeutic strategies.
Assuntos
Doença de Crohn , Fusobacterium nucleatum , Periodontite , Porphyromonas gingivalis , Humanos , Doença de Crohn/microbiologia , Doença de Crohn/complicações , Periodontite/microbiologia , Periodontite/complicações , Animais , Camundongos , Masculino , Feminino , Adulto , Fusobacterium nucleatum/isolamento & purificação , Células CACO-2 , Saliva/microbiologia , RNA Ribossômico 16SRESUMO
PURPOSE: To characterize the bacterial community in the primarily infected root canals. METHODS: A total of 13 samples were collected from the primarily infected root canals. 16 S rDNA sequencing was performed to define bacterial community. Taxonomic annotation, bacterial hierarchical structures, community richness and diversity, and inter-subject variability of the bacterial community in the root canal samples were analyzed. Gender, age, and duration of the toothache-specific bacterial community associated with the patient groups were analyzed. RESULTS: A total of 359 Species were annotated and identified in the whole study cohort. The Alpha diversity analysis showed that the species diversity and detection rate of the 13 samples were high, which reflected the authenticity of sequencing results. The Beta diversity analysis was used to compare the degree of difference between different root canal samples. The 13 samples were divided into two groups according to the results, group A was samples I1-I12, and group B was samples I13. The bacterial species of group A samples were analyzed with the clinical characteristics of patients, and it was found that gender, and duration specific differences in bacterial species, and there was no significant difference in species types among different ages of patients. CONCLUSION: There were a wide diversity and inter-subject variability in the bacterial community in the primary infected root canals. While Porphyromonas gingivalis was the most abundant species, Fusobacterium nucleatum was the most variable species in the bacterial community of the root canal. The bacterial community at different taxonomic levels varied from sample to sample, despite consistent disease diagnoses. There was gender, duration-specific differences in the bacterial species in the primary infected root canals.
Assuntos
Cavidade Pulpar , Periodontite Periapical , Humanos , Cavidade Pulpar/microbiologia , População do Leste Asiático , Fusobacterium nucleatum/genética , Fusobacterium nucleatum/isolamento & purificação , Periodontite Periapical/microbiologia , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/isolamento & purificação , Tratamento do Canal Radicular , DNA RibossômicoRESUMO
Dysbiosis of oral microbiome may dictate the progression of oral squamous cell carcinoma (OSCC). Yet, the composition of oral microbiome fluctuates by saliva and distinct sites of oral cavity and is affected by risky behaviors (smoking, drinking and betel quid chewing) and individuals' oral health condition. To characterize the disturbances in the oral microbial population mainly due to oral tumorigenicity, we profiled the bacteria within the surface of OSCC lesion and its contralateral normal tissue from discovery (n = 74) and validation (n = 42) cohorts of male patients with cancers of the buccal mucosa. Significant alterations in the bacterial diversity and relative abundance of specific oral microbiota (most profoundly, an enrichment for genus Fusobacterium and the loss of genus Streptococcus in the tumor sites) were identified. Functional prediction of oral microbiome shown that microbial genes related to the metabolism of terpenoids and polyketides were differentially enriched between the control and tumor groups, indicating a functional role of oral microbiome in formulating a tumor microenvironment via attenuated biosynthesis of secondary metabolites with anti-cancer effects. Furthermore, the vast majority of microbial signatures detected in the discovery cohort was generalized well to the independent validation cohort, and the clinical validity of these OSCC-associated microbes was observed and successfully replicated. Overall, our analyses reveal signatures (a profusion of Fusobacterium nucleatum CTI-2 and a decrease in Streptococcus pneumoniae) and functions (decreased production of tumor-suppressive metabolites) of oral microbiota related to oral cancer.
Assuntos
Disbiose/imunologia , Detecção Precoce de Câncer/métodos , Microbiota/imunologia , Mucosa Bucal/microbiologia , Neoplasias Bucais/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Adulto , Idoso , Estudos de Coortes , DNA Bacteriano/isolamento & purificação , Progressão da Doença , Disbiose/diagnóstico , Disbiose/microbiologia , Disbiose/patologia , Fusobacterium nucleatum/genética , Fusobacterium nucleatum/imunologia , Fusobacterium nucleatum/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Neoplasias Bucais/imunologia , Neoplasias Bucais/microbiologia , Neoplasias Bucais/patologia , Prognóstico , RNA Ribossômico 16S/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/isolamento & purificação , Microambiente Tumoral/imunologiaRESUMO
We report 4 cases of Fusobacterium nucleatum bacteremia associated with coronavirus disease (COVID-19). Three cases occurred concomitantly with COVID-19 diagnosis; 1 occurred on day 15 of intensive care. None of the patients had known risk factors for F. nucleatum bacteremia. F. nucleatum infection could represent a possible complication of COVID-19.
Assuntos
COVID-19/complicações , Infecções por Fusobacterium/complicações , Adulto , Idoso , Bacteriemia , Bélgica , COVID-19/epidemiologia , Fusobacterium nucleatum/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Fusobacterium nucleatum has been detected in 8%-13% of human colorectal cancer, and shown to inhibit immune responses against primary colorectal tumors in animal models. Thus, we hypothesized that the presence of F. nucleatum might be associated with reduced T cell density in colorectal cancer liver metastases (CRLM). We quantified F. nucleatum DNA in 181 CRLM specimens using quantitative PCR assay. The densities of CD8+ T cells, CD33+ cells (marker for myeloid-derived suppressor cells [MDSCs]), and CD163+ cells (marker for tumor-associated macrophages [TAMs]) in CRLM tissue were determined by immunohistochemical staining. Fusobacterium nucleatum was detected in eight (4.4%) of 181 CRLM specimens. Compared with F. nucleatum-negative CRLM, F. nucleatum-positive CRLM showed significantly lower density of CD8+ T cells (P = .033) and higher density of MDSCs (P = .001). The association of F. nucleatum with the density of TAMs was not statistically significant (P = .70). The presence of F. nucleatum is associated with a lower density of CD8+ T cells and a higher density of MDSCs in CRLM tissue. Upon validation, our findings could provide insights to develop strategies that involve targeting microbiota and immune cells for the prevention and treatment of CRLM.
Assuntos
Linfócitos T CD8-Positivos/citologia , Neoplasias Colorretais/microbiologia , Fusobacterium nucleatum/imunologia , Neoplasias Hepáticas/imunologia , Neoplasias Colorretais/patologia , DNA Bacteriano/análise , Feminino , Fusobacterium nucleatum/genética , Fusobacterium nucleatum/isolamento & purificação , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/microbiologia , Neoplasias Hepáticas/secundário , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/citologia , Macrófagos Associados a Tumor/citologiaRESUMO
BACKGROUND: High levels of periodontopathic bacteria as well as Streptococcus anginosus were detected in cancer tissue from patients with esophageal cancer. An association between oral infectious bacteria and esophageal cancer has been reported. METHODS: Characteristics of the oral microbiota and periodontal conditions were studied as clinicopathologic factors in patients with esophageal cancer. The study included 61 patients with esophageal cancer and 62 matched individuals without any cancers. Samples of subgingival dental plaque and unstimulated saliva were collected to evaluate the prevalence and abundance of the following oral bacteria using a real-time polymerase chain reaction assay: Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, Treponema denticola, and S. anginosus. RESULTS: In the cancer group, the prevalence of all bacteria, with the exception of F. nucleatum, in dental plaque; the prevalence of A. actinomycetemcomitans in saliva; the abundance of all bacteria, with the exception of F. nucleatum and P. intermedia, in dental plaque; and the abundance of A. actinomycetemcomitans and S. anginosus in saliva were significantly higher. Furthermore, a logistic regression analysis suggested that the prevalence of T. forsythia and S. anginosus in dental plaque and of A. actinomycetemcomitans in saliva, as well as a drinking habit, were associated with a high risk of esophageal cancer, with a high odds ratio. CONCLUSIONS: The current findings have potential implications for the early diagnosis of esophageal cancer.
Assuntos
Placa Dentária/microbiologia , Neoplasias Esofágicas/microbiologia , Boca/microbiologia , Saliva/microbiologia , Adulto , Idoso , Aggregatibacter actinomycetemcomitans , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etiologia , Feminino , Fusobacterium nucleatum/isolamento & purificação , Fusobacterium nucleatum/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Porphyromonas gingivalis/isolamento & purificação , Porphyromonas gingivalis/patogenicidade , Prevotella intermedia/isolamento & purificação , Prevotella intermedia/patogenicidade , Fatores de Risco , Streptococcus anginosus/isolamento & purificação , Streptococcus anginosus/patogenicidade , Tannerella forsythia/isolamento & purificação , Tannerella forsythia/patogenicidade , Treponema denticola/isolamento & purificação , Treponema denticola/patogenicidadeRESUMO
Epidemiological data have shown that periodontal bacterial infection, periodontitis, and oral squamous cell carcinoma have close relationship on the disease progress and risk. However, the specific role of periodontal microbes and their mechanism in the development of oral squamous cell carcinoma is not yet clear. In our previous work, metagenomic Illumina Mi-seq analysis was used to identify tstructure and abundance of periodontital microbiome. Accoding to the results, we used Porphyromonas.spp. and Fusobacterium.spp. as the periodontitis positive microbiota; Neisseria.spp and Corynebacterium.spp as periodontitis negative microbiota (their average relative abundance were >5%). These representative strains of the above genus were used to infect OSCC cells to explore their effect on tumor cell biology behavior, and detect the expression level of the gene in related to inflammation, migration, invasion and cell cycle. We find that periodontitis positive correlated microbiota had a promoting effect on the development of oral squamous cell carcinoma in vitro by regulating mRNA and protein expression of IL-6, IL-8, MMP-9 and Cyclin-D1. Periodontitis negative correlated microbiota had suppression effect on the development of oral squamous cell carcinoma in vitro analysis.
Assuntos
Neoplasias de Cabeça e Pescoço/microbiologia , Microbiota , Periodontite/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Infecções por Bacteroidaceae/complicações , Infecções por Bacteroidaceae/microbiologia , Infecções por Bacteroidaceae/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Corynebacterium/genética , Corynebacterium/isolamento & purificação , Infecções por Fusobacterium/complicações , Infecções por Fusobacterium/microbiologia , Infecções por Fusobacterium/patologia , Fusobacterium nucleatum/genética , Fusobacterium nucleatum/isolamento & purificação , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neisseria sicca/genética , Neisseria sicca/isolamento & purificação , Infecções por Neisseriaceae/complicações , Infecções por Neisseriaceae/microbiologia , Infecções por Neisseriaceae/patologia , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/isolamento & purificação , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in China. The role of the bacteria present in ESCC tissue in neoplastic progression has not been fully elucidated. This study aimed to uncover different bacterial communities in ESCC tissues and examine the correlation between the abundance of the esophageal flora and clinicopathologic characteristics of ESCC. RESULTS: Microorganisms in tumors and normal tissues showed obvious clustering characteristics. The abundance of Fusobacterium (P = 0.0052) was increased in tumor tissues. The high level of Fusobacterium nucleatum was significantly associated with pT stage (P = 0.039) and clinical stage (P = 0.0039). The WES data showed that COL22A1, TRBV10-1, CSMD3, SCN7A and PSG11 were present in only the F. nucleatum-positive ESCC samples. GO and protein domain enrichment results suggested that epidermal growth factor might be involved in the regulation of cell apoptosis in F. nucleatum-positive ESCC. Both a higher mutational burden and F. nucleatum-positive was observed in tumors with metastasis than in tumors without metastasis. CONCLUSION: F. nucleatum is closely related to the pT stage and clinical stage of ESCC. The abundance of F. nucleatum and tumor mutation burden may be used in combination as a potential method to predict metastasis in ESCC.
Assuntos
Neoplasias Esofágicas/microbiologia , Carcinoma de Células Escamosas do Esôfago/microbiologia , Esôfago/microbiologia , Fusobacterium nucleatum/isolamento & purificação , Idoso , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , China , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Esôfago/patologia , Esôfago/cirurgia , Feminino , Fusobacterium nucleatum/classificação , Fusobacterium nucleatum/genética , Fusobacterium nucleatum/crescimento & desenvolvimento , Humanos , Masculino , Microbiota , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos RetrospectivosRESUMO
While the impact of oral microbiome dysbiosis on autoimmune diseases has been partially investigated, its role on bullous diseases like Pemphigus Vulgaris (PV) is a totally unexplored field. This study aims to present the composition and relative abundance of microbial communities in both healthy individuals and patients with oral PV lesions. Ion Torrent was used to apply deep sequencing of the bacterial 16S rRNA gene to oral smear samples of 15 healthy subjects and 15 patients. The results showed that the most dominant phyla were Firmicutes (55.88% controls-c vs 61.27% patients-p, p value = 0.002), Proteobacteria (9.17%c vs 12.33%p, p value = 0.007) and Fusobacteria (3.39%c vs 4.09%p, p value = 0.03). Alpha diversity showed a significant difference in the number of genera between patients and controls (p value = 0.04). Beta diversity showed statistical differences in the microbial community composition between two groups. Fusobacterium nucleatum, Gemella haemolysans and Parvimonas micra were statistically abundant in patients. We noticed the characteristic fetor coming out of oral PV lesions. Most of anaerobic bacteria responsible for oral halitosis are periopathogenic. Though, only F. nucleatum and P. micra were differentially abundant in our patients. Especially, F. nucleatum has been reported many times as responsible for bad breath. Furthermore, Streptococcus salivarius and Rothia mucilaginosa, species mostly associated with clean breath, were found in relative abundance in the healthy group. Consequently, the distinct malodor observed in PV patients might be attributed either to the abundance of F. nucleatum and P. micra and/or to the lower levels of S. salivarius and R. mucilanginosa in oral lesions.
Assuntos
Firmicutes/isolamento & purificação , Fusobacterium nucleatum/isolamento & purificação , Gemella/isolamento & purificação , Micrococcaceae/isolamento & purificação , Boca/microbiologia , Pênfigo/microbiologia , Disbiose/microbiologia , Firmicutes/genética , Fusobacterium nucleatum/genética , Gemella/genética , Halitose/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Microbiota/genética , Micrococcaceae/genética , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Adulto JovemRESUMO
BACKGROUND: Intrauterine infection accounts for a quarter of the cases of spontaneous preterm birth; however, at present, it is not possible to efficiently identify pregnant women at risk to deliver preventative treatments. OBJECTIVE: This study aimed to establish a vaginal microbial DNA test for Australian women in midpregnancy that will identify those at increased risk of spontaneous preterm birth. STUDY DESIGN: A total of 1000 women with singleton pregnancies were recruited in Perth, Australia. Midvaginal swabs were collected between 12 and 23 weeks' gestation. DNA was extracted for the detection of 23 risk-related microbial DNA targets by quantitative polymerase chain reaction. Obstetrical history, pregnancy outcome, and demographics were recorded. RESULTS: After excluding 64 women owing to losses to follow-up and insufficient sample for microbial analyses, the final cohort consisted of 936 women of predominantly white race (74.3%). The overall preterm birth rate was 12.6% (118 births); the spontaneous preterm birth rate at <37 weeks' gestation was 6.2% (2.9% at ≤34 weeks' gestation), whereas the preterm premature rupture of the membranes rate was 4.2%. No single individual microbial target predicted increased spontaneous preterm birth risk. Conversely, women who subsequently delivered at term had higher amounts of Lactobacillus crispatus, Lactobacillus gasseri, or Lactobacillus jensenii DNA in their vaginal swabs (13.8% spontaneous preterm birth vs 31.2% term; P=.005). In the remaining women, a specific microbial DNA signature was identified that was strongly predictive of spontaneous preterm birth risk, consisting of DNA from Gardnerella vaginalis (clade 4), Lactobacillus iners, and Ureaplasma parvum (serovars 3 and 6). Risk prediction was improved if Fusobacterium nucleatum detection was included in the test algorithm. The final algorithm, which we called the Gardnerella Lactobacillus Ureaplasma (GLU) test, was able to detect women at risk of spontaneous preterm birth at <37 and ≤34 weeks' gestation, with sensitivities of 37.9% and 44.4%, respectively, and likelihood ratios (plus or minus) of 2.22 per 0.75 and 2.52 per 0.67, respectively. Preterm premature rupture of the membranes was more than twice as common in GLU-positive women. Adjusting for maternal demographics, ethnicity, and clinical history did not improve prediction. Only a history of spontaneous preterm birth was more effective at predicting spontaneous preterm birth than a GLU-positive result (odds ratio, 3.6). CONCLUSION: We have identified a vaginal bacterial DNA signature that identifies women with a singleton pregnancy who are at increased risk of spontaneous preterm birth and may benefit from targeted antimicrobial therapy.
Assuntos
DNA Bacteriano/análise , Ruptura Prematura de Membranas Fetais/epidemiologia , Microbiota/genética , Nascimento Prematuro/epidemiologia , Nascimento a Termo , Vagina/microbiologia , Adulto , Austrália , Feminino , Ruptura Prematura de Membranas Fetais/microbiologia , Fusobacterium nucleatum/genética , Fusobacterium nucleatum/isolamento & purificação , Gardnerella vaginalis/genética , Gardnerella vaginalis/isolamento & purificação , Humanos , Lactobacillus/genética , Lactobacillus/isolamento & purificação , Lactobacillus crispatus/genética , Lactobacillus crispatus/isolamento & purificação , Lactobacillus gasseri/genética , Lactobacillus gasseri/isolamento & purificação , Gravidez , Segundo Trimestre da Gravidez , Nascimento Prematuro/microbiologia , Risco , Ureaplasma/genética , Ureaplasma/isolamento & purificação , Adulto JovemRESUMO
Accumulating evidence links Fusobacterium nucleatum with ulcerative colitis (UC). The mechanism by which F. nucleatum promotes intestinal inflammation in UC remains poorly defined. Here, we first examined the abundance and impact of F. nucleatum on disease activity in UC tissues. Next, we isolated a strain of F. nucleatum from UC tissues and explored whether F. nucleatum aggravates the intestinal inflammatory response in vitro and in vivo. We also examined whether F. nucleatum infection involves the NF-κB or IL-17F signaling pathways. Our data showed that F. nucleatum was enriched in 51.78% of UC tissues and was correlated with the clinical course, clinical activity and refractory behavior of UC (p < 0.05). Furthermore, we demonstrated that F. nucleatum promoted intestinal epithelial damage and the expression of the inflammatory cytokines IL-1ß, Il-6, IL-17F and TNF-α. Mechanistically, F. nucleatum targeted caspase activation and recruitment domain 3 (CARD3) through NOD2 to activate the IL-17F/NF-κB pathway in vivo and in vitro. Thus, F. nucleatum orchestrates a molecular network involving CARD3 and IL-17F to control the UC process. Measuring and targeting F. nucleatum and its associated pathways will yield valuable insight into the prevention and treatment of UC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Assuntos
Colite Ulcerativa/microbiologia , Infecções por Fusobacterium/complicações , Fusobacterium nucleatum/patogenicidade , Interleucina-17/metabolismo , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/biossíntese , Adolescente , Adulto , Idoso , Animais , Estudos de Casos e Controles , Células Cultivadas , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Feminino , Infecções por Fusobacterium/metabolismo , Fusobacterium nucleatum/isolamento & purificação , Humanos , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , NF-kappa B/metabolismo , RNA Mensageiro/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/deficiência , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/fisiologia , Índice de Gravidade de Doença , Transdução de Sinais/fisiologia , Regulação para Cima/fisiologia , Adulto JovemRESUMO
The role of Fusobacterium nucleatum, often associated with intestinal diseases, in the remission of dextran sulfate sodium (DSS)-induced colitis was investigated. Female mice were divided into groups DC (DSS control) and DF (DSS + F. nucleatum). F. nucleatum (1.0 × 1010 cfu/mouse/day) in phosphate-buffered saline (PBS) was orally given to DF, while DC had PBS only. All mice had DSS in drinking water. In Experiment 1, mice underwent 2 inflammation phases, an in-between recovery phase and had their disease activity indices (DAI) calculated. Experiment 2 was similarly conducted, except that mice were dissected 3 days postrecovery, and had blood and colonic mucosal samples collected. In Experiment 1, DF had significantly (P < .05) higher DAI than DC, during the recovery and 2nd inflammation phases. In Experiment 2, genus Bacteroides was significantly (P < .05) higher and family Lachnospiraceae significantly lower in cecal mucosa-associated microbiota of DF than in that of DC. We concluded that F. nucleatum can impede colitis remission.
Assuntos
Colite/microbiologia , Colo/microbiologia , Fusobacterium nucleatum/patogenicidade , Mucosa Intestinal/microbiologia , Actinobacteria/genética , Actinobacteria/crescimento & desenvolvimento , Actinobacteria/isolamento & purificação , Animais , Bacteroidetes/genética , Bacteroidetes/crescimento & desenvolvimento , Bacteroidetes/isolamento & purificação , Colite/induzido quimicamente , Colite/patologia , Colo/patologia , Convalescença , Sulfato de Dextrana/administração & dosagem , Modelos Animais de Doenças , Feminino , Firmicutes/genética , Firmicutes/crescimento & desenvolvimento , Firmicutes/isolamento & purificação , Fusobacterium nucleatum/crescimento & desenvolvimento , Fusobacterium nucleatum/isolamento & purificação , Microbioma Gastrointestinal/genética , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos C57BL , Permeabilidade , Proteobactérias/genética , Proteobactérias/crescimento & desenvolvimento , Proteobactérias/isolamento & purificação , RNA Bacteriano/genéticaRESUMO
A 42-year-old man was referred to the Department of Orthopedic Surgery with pain over his right greater trochanter and signs of systemic infection. CT showed an enhanced mass in his gluteus maximus as well as gas in the biceps femoris over the underlying hip joint. Tissue biopsy yielded Fusobacterium nucleatum and Actinomyces turicensis. The patient was successfully treated for 6 weeks with amoxicillin/clavulanic acid 875mg/125mg and metronidazole 500mg.