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1.
BMC Oral Health ; 23(1): 932, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012618

RESUMO

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 Ribossômico
2.
PLoS One ; 17(1): e0262416, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34995318

RESUMO

BACKGROUND: Mucosal infiltration by certain bacterial species may contribute to the development and progression of colorectal cancer (CRC). There is considerable variation in reported detection rates in human CRC samples and the extent to which bacterial infiltration varies across regions of the primary tumour is unknown. This study aimed to determine if there is an optimal site for bacterial detection within CRC tumours. METHODS: Presence of target bacterial species was assessed by quantitative real-time PCR (qPCR) in 42 human CRC tumours. Abundance in primary tumour regions, normal epithelium and at metastatic sites was investigated in an expanded cohort of 51 patients. Species presence/absence was confirmed by diversity profiling in five patients. Correlation with total bacterial load and clinicopathological features was assessed. RESULTS: Fusobacterium nucleatum and Bacteroides fragilis were detected in tumours from 43% and 24% of patients, respectively (17% positive for both species). The optimal detection site was the tumour luminal surface (TLS). Patients testing positive at the TLS frequently tested negative at other sites, including central tumour and invasive margin. F. nucleatum was detected at a higher frequency in tumour versus normal epithelium (p < 0.01) and was associated with more advanced disease (p = 0.01). Detection of both species correlated with total bacterial load. However, corroboration of qPCR results via diversity profiling suggests detection of these species may indicate a specific microbial signature. CONCLUSIONS: This study supports a role for F. nucleatum in CRC development. Presence of F. nucleatum and B. fragilis varies across primary tumour regions, with the TLS representing the optimal site for bacterial detection.


Assuntos
Infecções por Bacteroides/complicações , Bacteroides fragilis/isolamento & purificação , Neoplasias Colorretais/microbiologia , Infecções por Fusobacterium/complicações , Fusobacterium nucleatum/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carga Bacteriana , Infecções por Bacteroides/diagnóstico , Neoplasias Colorretais/etiologia , Feminino , Infecções por Fusobacterium/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade
3.
Clin Transl Gastroenterol ; 12(11): e00424, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34797780

RESUMO

INTRODUCTION: The genomic characterization of primary nonampullary duodenal adenocarcinoma indicates a genetic resemblance to gastric and colorectal cancers. However, a correlation between the clinical and molecular characteristics of these cancers has not been established. This study aimed to elucidate the clinicopathological features of sporadic nonampullary duodenal epithelial tumors, including their molecular characteristics and prognostic factors. METHODS: One hundred forty-eight patients with sporadic nonampullary duodenal epithelial tumors were examined in this study. Patient sex, age, TNM stage, tumor location, treatment methods, histology, KRAS mutation, BRAF mutation, Fusobacterium nucleatum, mucin phenotype, and programmed death-ligand 1 (PD-L1) status were evaluated. KRAS and BRAF mutations, Fusobacterium nucleatum, mucin phenotype, and PD-L1 status were analyzed by direct sequencing, quantitative polymerase chain reaction, and immunochemical staining. RESULTS: The median follow-up duration was 119.4 months. There were no deaths from duodenal adenoma (the primary disease). Kaplan-Meier analysis for duodenal adenocarcinoma showed a significant effect of TNM stage (P < 0.01). In univariate analysis of primary deaths from duodenal adenocarcinoma, TNM stage II or higher, undifferentiated, KRAS mutations, gastric phenotype, intestinal phenotype, and PD-L1 status were significant factors. In multivariate analysis, TNM stage II or higher (hazard ratio: 1.63 × 1010, 95% confidence interval: 18.66-6.69 × 1036) and KRAS mutation (hazard ratio: 3.49, confidence interval: 1.52-7.91) were significant factors. DISCUSSION: Only KRAS mutation was a significant prognostic factor in primary sporadic nonampullary duodenal adenocarcinoma in cases in which TNM stage was considered.


Assuntos
Adenocarcinoma/genética , Neoplasias Duodenais/genética , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/análise , Neoplasias Duodenais/microbiologia , Neoplasias Duodenais/patologia , Feminino , Fusobacterium nucleatum/isolamento & purificação , Mucosa Gástrica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Proteínas Proto-Oncogênicas B-raf/genética
4.
Sci Rep ; 11(1): 20263, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642332

RESUMO

Recent evidence suggests that Fusobacterium nucleatum (Fn) is associated with the development and progression of colorectal cancer. We aimed to delineate the clinical implications of Fn in metastatic colon cancer. We performed quantitative polymerase chain reaction (qPCR) using DNA samples from synchronous metastatic colon cancer patients with either formalin-fixed paraffin-embedded (FFPE) archival primary site tumor samples or fresh colon tissues. Progression-free survival (PFS)1 and PFS2 were defined as PFS of first- and second-line palliative settings. qPCR for Fn was successfully performed using 112 samples (FFPE, n = 61; fresh tissue, n = 51). Forty-one and 68 patients had right-sided and left-sided colon cancer, respectively. Patients with Fn enriched right-sided colon cancers had shorter PFS1 (9.7 vs. 11.2 months) than the other subgroups (HR 3.54, 95% confidence interval [CI] 1.05-11.99; P = 0.04). Fn positive right-sided colon was also associated with shorter PFS2 (3.7 vs. 6.7 months; HR 2.34, 95% CI 0.69-7.91; P = 0.04). In the univariate analysis, PFS1 was affected by differentiation and Fn positive right-sided colon cancer. The multivariate analysis showed that differentiation (HR 2.68, 95% CI 1.40-5.14, P = 0.01) and Fn positive right-sided colon (HR 0.40, 95% CI 0.18-0.88, P = 0.02) were associated with PFS1. Fn enrichment in right sided colon was not associated with overall survival (OS). Fn enrichment has significantly worse prognosis in terms of PFS1 and PFS2 in patients with right-sided metastatic colon cancers.


Assuntos
Neoplasias do Colo/microbiologia , DNA Bacteriano/genética , Infecções por Fusobacterium/diagnóstico , Fusobacterium nucleatum/isolamento & purificação , Neoplasias Primárias Múltiplas/microbiologia , Neoplasias do Colo/patologia , DNA Ribossômico/genética , Feminino , Fusobacterium nucleatum/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Metástase Neoplásica , Prognóstico , Intervalo Livre de Progressão , RNA Ribossômico 16S/genética
5.
BMC Microbiol ; 21(1): 301, 2021 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717543

RESUMO

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 Retrospectivos
6.
Biochem Biophys Res Commun ; 576: 80-85, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34482027

RESUMO

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/patologia
7.
Cancer Sci ; 112(11): 4470-4477, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34464993

RESUMO

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/citologia
8.
Anaerobe ; 71: 102420, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34314865

RESUMO

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.


Assuntos
Actinomycetaceae/isolamento & purificação , Infecções por Actinomycetales/microbiologia , Bacteriemia/microbiologia , COVID-19/imunologia , Infecções por Fusobacterium/microbiologia , Fusobacterium nucleatum/isolamento & purificação , Quadril/microbiologia , Abscesso/tratamento farmacológico , Abscesso/microbiologia , Actinomycetaceae/efeitos dos fármacos , Actinomycetaceae/genética , Infecções por Actinomycetales/tratamento farmacológico , Adulto , Antibacterianos/uso terapêutico , COVID-19/virologia , Infecções por Fusobacterium/tratamento farmacológico , Fusobacterium nucleatum/efeitos dos fármacos , Fusobacterium nucleatum/genética , Humanos , Hospedeiro Imunocomprometido , Masculino , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação
9.
Eur Rev Med Pharmacol Sci ; 25(13): 4579-4596, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34286500

RESUMO

OBJECTIVE: The human being has evolved in close symbiosis with its own ecological community of commensal, symbiotic and pathogenic bacteria. After the intestinal microbiome, that of the oral cavity is the largest and most diversified. Its importance is reflected not only in local and systemic diseases, but also in pregnancy since it would seem to influence the placental microbiome. MATERIALS AND METHODS: This is a literature review of articles published in PubMed about Fusobacterium Nucleatum and both its implications with systemic and oral health, adverse pregnancy outcomes, flavors perception and its interference in the oral-nasal mucosal immunity. RESULTS: It is in maintaining the microbiome's homeostasis that the Fusobacterium nucleatum, an opportunistic periodontal pathogen of the oral cavity, plays a crucial role both as a bridge microorganism of the tongue biofilm, and in maintaining the balance between the different species in the oral-nasal mucosal immunity also by taste receptors interaction. It is also involved in the flavor perception and its detection in the oral microbiome of children from the first days of life suggests a possible physiological role. However, the dysbiosis can determine its pathogenicity with local and systemic consequences, including the pathogenesis of respiratory infections. CONCLUSIONS: It is interesting to evaluate its possible correlation with Sars-CoV-2 and the consequences on the microflora of the oral cavity, both to promote a possible broad-spectrum preventive action, in favor of all subjects for whom, by promoting the eubiosis of the oral microbiome, a defensive action could be envisaged by the commensals themselves but, above all, for patients with specific comorbidities and therefore already prone to oral dysbiosis.


Assuntos
COVID-19/microbiologia , Fusobacterium nucleatum/isolamento & purificação , Boca/microbiologia , COVID-19/imunologia , Feminino , Fusobacterium nucleatum/imunologia , Fusobacterium nucleatum/patogenicidade , Humanos , Boca/imunologia , Gravidez
10.
Andes Pediatr ; 92(1): 93-98, 2021 Feb.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34106188

RESUMO

INTRODUCTION: Fusobacterium nucleatum is an anaerobic bacillus that is part of the oral microbiota and dental pla que. This can cause local and potentially remote infections, which are exceptional in pediatrics. Ob jective: To present the case of a patient with lung injury with chest wall invasion by Fusobacterium nucleatum. CLINICAL CASE: An 11-year-old female immunocompetent patient who consulted due to a two-week history of cough, night sweats, without fever or weight loss, and increased volume at the left spleen thoracic level. There was no history of chest wall trauma or travel outside the country. Two weeks before the onset of symptoms, she was treated for dental caries. Imaging studies and CT scan showed left spleen pneumonia, which invades the pleura and the chest wall. A minimal thoracotomy was performed, releasing a thick, foul-smelling liquid. The studies for common germs and tubercu losis were negative. Hematology ruled out tumor lesions. The anaerobic study reported the develo pment of Fusobacterium nucleatum. The patient was treated with penicillin followed by amoxicillin presenting good clinical and radiological responses. The dental procedure was suspected as the cause of infection. CONCLUSIONS: Fusobacterium nucleatum can occasionally cause remote or extra-oral in fections in immunocompetent patients, such as pneumonia with chest wall invasion, therefore it is necessary to bear it in mind.


Assuntos
Infecções por Fusobacterium , Fusobacterium nucleatum/isolamento & purificação , Pneumonia Bacteriana/microbiologia , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Criança , Cárie Dentária/complicações , Cárie Dentária/terapia , Feminino , Infecções por Fusobacterium/diagnóstico por imagem , Infecções por Fusobacterium/tratamento farmacológico , Infecções por Fusobacterium/cirurgia , Humanos , Penicilinas/uso terapêutico , Pneumonia Bacteriana/diagnóstico por imagem , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/cirurgia , Parede Torácica/microbiologia , Toracotomia
11.
Theranostics ; 11(14): 6703-6716, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093848

RESUMO

Rationale: The endemic of peri-implantitis affects over 25% of dental implants. Current treatment depends on empirical patient and site-based stratifications and lacks a consistent risk grading system. Methods: We investigated a unique cohort of peri-implantitis patients undergoing regenerative therapy with comprehensive clinical, immune, and microbial profiling. We utilized a robust outlier-resistant machine learning algorithm for immune deconvolution. Results: Unsupervised clustering identified risk groups with distinct immune profiles, microbial colonization dynamics, and regenerative outcomes. Low-risk patients exhibited elevated M1/M2-like macrophage ratios and lower B-cell infiltration. The low-risk immune profile was characterized by enhanced complement signaling and higher levels of Th1 and Th17 cytokines. Fusobacterium nucleatum and Prevotella intermedia were significantly enriched in high-risk individuals. Although surgery reduced microbial burden at the peri-implant interface in all groups, only low-risk individuals exhibited suppression of keystone pathogen re-colonization. Conclusion: Peri-implant immune microenvironment shapes microbial composition and the course of regeneration. Immune signatures show untapped potential in improving the risk-grading for peri-implantitis.


Assuntos
Linfócitos B/imunologia , Citocinas/metabolismo , Aprendizado de Máquina , Macrófagos/imunologia , Microbiota/genética , Peri-Implantite/imunologia , Peri-Implantite/microbiologia , Algoritmos , Estudos de Coortes , Fusobacterium nucleatum/isolamento & purificação , Humanos , Imunofenotipagem , Peri-Implantite/classificação , Prevotella intermedia/isolamento & purificação , Fatores de Risco , Células Th1/metabolismo , Células Th17/metabolismo
12.
PLoS One ; 16(4): e0251017, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33914825

RESUMO

BACKGROUND: Certain oral bacterial pathogens may play a role in oral carcinogenesis. We assessed the feasibility of conducting a population-based study in India to examine the distributions and levels of Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia in relation to oral leukoplakia (a potentially malignant disorder) and other participant characteristics. METHODS: This exploratory case-control study was nested within a large urban Indian cohort and the data included 22 men and women with oral leukoplakia (cases) and 69 leukoplakia-free controls. Each participant provided a salivary rinse sample, and a subset of 34 participants (9 cases; 25 controls) also provided a gingival swab sample from keratinized gingival surface for quantitative polymerase chain reaction (qPCR). RESULTS: Neither the distribution nor the levels of pathogens were associated with oral leukoplakia; however, individual pathogen levels were more strongly correlated with each other in cases compared to controls. Among controls, the median level of total pathogens was the highest (7.55×104 copies/ng DNA) among persons of low socioeconomic status. Salivary rinse provided better DNA concentration than gingival swab for qPCR analysis (mean concentration: 1.8 ng/µl vs. 0.2 ng/µl). CONCLUSIONS: This study confirms the feasibility of population studies evaluating oral microbiome in low-resource settings and identifies promising leads for future research.


Assuntos
DNA Bacteriano/genética , Fusobacterium nucleatum/isolamento & purificação , Leucoplasia Oral/microbiologia , Porphyromonas gingivalis/isolamento & purificação , Prevotella intermedia/isolamento & purificação , Adulto , Estudos de Casos e Controles , Países em Desenvolvimento , Estudos de Viabilidade , Feminino , Fusobacterium nucleatum/genética , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Porphyromonas gingivalis/genética , Prevotella intermedia/genética , Saliva/microbiologia , População Urbana
13.
Sci Rep ; 11(1): 7870, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846399

RESUMO

Changes in the oral microbiome, particularly Fusobacterium nucleatum, are associated with oral squamous cell carcinoma (OSCC). F. nucleatum has been reported to modulate local immunity in cancers. We aimed to assess the association between intratumoral F. nucleatum and clinico-pathological features, relapse, and overall survival (OS) in two independent cohorts of patients with OSCC, and to explore the interplay with immune-related genes. We retrospectively analyzed tissue samples from a first cohort of 122 patients with head and neck squamous cell carcinoma, including 61 OSCC (cohort #1), and a second cohort of 90 additional OSCC (cohort #2). We then performed a sensitivity analysis on the merged cohort of OSCC patients (N = 151). F. nucleatum 16S rRNA gene sequences were quantified using real-time quantitative PCR. The presence of gram-negative bacteria and macrophages was confirmed by LPS and CD163 immunostainings, respectively. F. nucleatum positivity was associated with older age, less alcohol and combined alcohol plus tobacco consumption, and less frequent lymph node invasion. There was a trend for a lower recurrence rate in F. nucleatum-positive cases, with less metastatic relapses compared to F. nucleatum-negative tumors, and significantly longer OS, relapse-free and metastasis-free survival. F. nucleatum status was independently associated with OS in multivariate analysis. Immune-related gene and immunohistochemistry analyses showed that gram-negative bacteria load inversely correlated with M2 macrophages. F. nucleatum-associated OSCC has a specific immune microenvironment, is more frequent in older, non-drinking patients, and associated with a favorable prognosis.


Assuntos
Fusobacterium nucleatum/isolamento & purificação , Microbioma Gastrointestinal , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Microambiente Tumoral , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia
14.
Biosci Biotechnol Biochem ; 85(5): 1235-1242, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33674867

RESUMO

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/genética
15.
Arch Microbiol ; 203(5): 2237-2247, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33634320

RESUMO

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 Jovem
16.
Sci Rep ; 11(1): 2925, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536501

RESUMO

Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.


Assuntos
Neoplasias Colorretais/diagnóstico , Disbiose/diagnóstico , Microbioma Gastrointestinal , Idoso , Akkermansia/isolamento & purificação , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias Colorretais/microbiologia , DNA Bacteriano/isolamento & purificação , Disbiose/complicações , Disbiose/microbiologia , Fezes/microbiologia , Feminino , Firmicutes/isolamento & purificação , Fusobacterium nucleatum/isolamento & purificação , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , Peptostreptococcus/isolamento & purificação , RNA Ribossômico 16S/genética
17.
Carcinogenesis ; 42(1): 127-135, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-32621740

RESUMO

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/imunologia
18.
Am J Obstet Gynecol ; 224(2): 206.e1-206.e23, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32861687

RESUMO

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 Jovem
19.
Emerg Infect Dis ; 27(3): 975-977, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33292922

RESUMO

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 Risco
20.
Cancer ; 127(4): 512-519, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33156979

RESUMO

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/patogenicidade
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