Oral microbial dysbiosis and its performance in predicting oral cancer

Abstract 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.

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Dysbiosis of Oral Microbiota During Oral Squamous Cell Carcinoma Development

Frontiers in Oncology ◽

10.3389/fonc.2021.614448 ◽

2021 ◽

Vol 11 ◽

Author(s):

Purandar Sarkar ◽

Samaresh Malik ◽

Sayantan Laha ◽

Shantanab Das ◽

Soumya Bunk ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cancer ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Indian Subcontinent ◽

Critical Role ◽

Oral Microbiome ◽

Oral Microbiota ◽

Microbial Composition

Infection with specific pathogens and alterations in tissue commensal microbial composition are intricately associated with the development of many human cancers. Likewise, dysbiosis of oral microbiome was also shown to play critical role in the initiation as well as progression of oral cancer. However, there are no reports portraying changes in oral microbial community in the patients of Indian subcontinent, which has the highest incidence of oral cancer per year, globally. To establish the association of bacterial dysbiosis and oral squamous cell carcinoma (OSCC) among the Indian population, malignant lesions and anatomically matched adjacent normal tissues were obtained from fifty well-differentiated OSCC patients and analyzed using 16S rRNA V3-V4 amplicon based sequencing on the MiSeq platform. Interestingly, in contrast to the previous studies, a significantly lower bacterial diversity was observed in the malignant samples as compared to the normal counterpart. Overall our study identified Prevotella, Corynebacterium, Pseudomonas, Deinococcus and Noviherbaspirillum as significantly enriched genera, whereas genera including Actinomyces, Sutterella, Stenotrophomonas, Anoxybacillus, and Serratia were notably decreased in the OSCC lesions. Moreover, we demonstrated HPV-16 but not HPV-18 was significantly associated with the OSCC development. In future, with additional validation, this panel could directly be applied into clinical diagnostic and prognostic workflows for OSCC in Indian scenario.

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Oral Microbiota and Salivary Levels of Oral Pathogens in Gastro-Intestinal Diseases: Current Knowledge and Exploratory Study

Microorganisms ◽

10.3390/microorganisms9051064 ◽

2021 ◽

Vol 9 (5) ◽

pp. 1064

Author(s):

Maria Contaldo ◽

Alessandra Fusco ◽

Paola Stiuso ◽

Stefania Lama ◽

Antonietta Gerarda Gravina ◽

...

Keyword(s):

Current Knowledge ◽

Fusobacterium Nucleatum ◽

Gastrointestinal Diseases ◽

Oral Microbiome ◽

Oral Microbiota ◽

Intestinal Diseases ◽

Non Invasive ◽

Invasive Method ◽

Oral Pathogens ◽

Bacterial Dna Extraction

Various bi-directional associations exist between oral health and gastro-intestinal diseases. The oral microbiome plays a role in the gastro-intestinal carcinogenesis and fusobacteria are the most investigated bacteria involved. This paper aims to review the current knowledge and report the preliminary data on salivary levels of Fusobacterium nucleatum, Porphyromonas gingivalis and Candida albicans in subjects with different gastro-intestinal conditions or pathologies, in order to determine any differences. The null hypothesis was “subjects with different gastro-intestinal diseases do not show significant differences in the composition of the oral microbiota”. Twenty-one subjects undergoing esophagastroduodenoscopy or colonscopy were recruited. For each subject, a salivary sample was collected before the endoscopy procedure, immediately stored at -20°C and subsequently used for genomic bacterial DNA extraction by real-time PCR. Low levels of F. nucleatum and P. gingivalis were peculiar in the oral microbiota in subjects affected by Helicobater pylori-negative chronic gastritis without cancerization and future studies will elucidate this association. The level of C. albicans did not statistically differ among groups. This preliminary study could be used in the future, following further investigation, as a non-invasive method for the search of gastrointestinal diseases and associated markers.

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The Oral Microbiota Is Modified by Systemic Diseases

Journal of Dental Research ◽

10.1177/0022034518805739 ◽

2018 ◽

Vol 98 (2) ◽

pp. 148-156 ◽

Cited By ~ 39

Author(s):

D.T. Graves ◽

J.D. Corrêa ◽

T.A. Silva

Keyword(s):

Lupus Erythematosus ◽

Leukocyte Adhesion ◽

Periodontal Diseases ◽

Oral Microbiome ◽

Tooth Surface ◽

Oral Microbiota ◽

Systemic Diseases ◽

Microbial Dysbiosis ◽

Inflammatory Drugs ◽

Periodontal Bone Loss

Periodontal diseases are initiated by bacteria that accumulate in a biofilm on the tooth surface and affect the adjacent periodontal tissue. Systemic diseases such as diabetes, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) increase susceptibility to destructive periodontal diseases. In human studies and in animal models, these diseases have been shown to enhance inflammation in the periodontium and increase the risk or severity of periodontitis. All 3 systemic diseases are linked to a decrease in bacterial taxa associated with health and an increase in taxa associated with disease. Although there is controversy regarding the specific oral bacterial changes associated with each disease, it has been reported that diabetes increases the levels of Capnocytophaga, Porphyromonas, and Pseudomonas, while Prevotella and Selenomonas are increased in RA and Selenomonas, Leptotrichia, and Prevotella in SLE. In an animal model, diabetes increased the pathogenicity of the oral microbiome, as shown by increased inflammation, osteoclastogenesis, and periodontal bone loss when transferred to normal germ-free hosts. Moreover, in diabetic animals, the increased pathogenicity could be substantially reversed by inhibition of IL-17, indicating that host inflammation altered the microbial pathogenicity. Increased IL-17 has also been shown in SLE, RA, and leukocyte adhesion deficiency and may contribute to oral microbial changes in these diseases. Successful RA treatment with anti-inflammatory drugs partially reverses the oral microbial dysbiosis. Together, these data demonstrate that systemic diseases characterized by enhanced inflammation disturb the oral microbiota and point to IL-17 as key mediator in this process.

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Smoking, Alcohol, and Betel Quid and Oral Cancer: A Prospective Cohort Study

Journal of Oncology ◽

10.1155/2011/525976 ◽

2011 ◽

Vol 2011 ◽

pp. 1-5 ◽

Cited By ~ 39

Author(s):

Wen-Jiun Lin ◽

Rong-San Jiang ◽

Shang-Heng Wu ◽

Fun-Jou Chen ◽

Shih-An Liu

Keyword(s):

Logistic Regression ◽

Oral Cancer ◽

Oral Cavity Cancer ◽

Betel Quid ◽

Multivariate Logistic Regression Model ◽

Multivariate Logistic Regression ◽

Cigarette Smokers ◽

Betel Quid Chewing ◽

Male Patients ◽

Oral Screening

We aimed to investigate the association between smoking, alcoholic consumption, and betel quid chewing with oral cancer in a prospective manner. All male patients age ≥18 years who visited our clinic received an oral mucosa inspection. Basic data including personal habits were also obtained. A multivariate logistic regression model was utilized to determine relevant risk factors for developing oral cavity cancer. A total of 10,657 participants were enrolled in this study. Abnormal findings were found in 514 participants (4.8%). Three hundred forty-four participants received biopsy, and 230 patients were proven to have oral cancer. The results of multivariate logistic regression found that those who smoked, consumed alcohol, and chewed betel quid on a regular basis were most likely to develop cancer (odds ratio: 46.87, 95% confidence interval: 31.84–69.00). Therefore, habitual cigarette smokers, alcohol consumers, and betel quid chewers have a higher risk of contracting oral cancer and should receive oral screening regularly so potential oral cancer can be detected as early as possible.

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Inhibitory effects of different medicinal plants on growth of some oral microbiome member

Medycyna Weterynaryjna ◽

10.21521/mw.6433 ◽

2020 ◽

Vol 76 (08) ◽

pp. 6433-2020

Author(s):

Zoran Tambur ◽

Biljana Miljković-Selimović ◽

Dolores Opačić ◽

Ema Aleksić ◽

Luka Ivančajić ◽

...

Keyword(s):

Hypericum Perforatum ◽

Public Health Problem ◽

Fusobacterium Nucleatum ◽

Oral Microbiome ◽

Thymus Vulgaris ◽

Oral Microbiota ◽

Acorus Calamus ◽

Inhibitory Effects ◽

Oral Infections ◽

Ethanol Extracts

Oral infections and dental caries are still considered as a serious public health problem. Using the method of minimum inhibitory concentrations (MICs), the aim of this study was to investigate the inhibitory effects of 16 plants on the growth of Actinomyces odontolyticus, Streptococcus mitis, Streptococcus sanguinis, Eikenella corrodens, Fusobacterium nucleatum, Lactobacillus acidophilus and Streptococcus mutans. The most effective were ethanol extracts of Rosmarinus officinalis, Salvia officinalis, Thymus vulgaris, Calendula officinalis and Hypericum perforatum. The least efficiency was observed for Acorus calamus extract. Plant extracts could be used in oral health as therapeutic and prophylactic approach or in balancing oral microbiota.

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Faculty Opinions recommendation of The Oral Microbiota May Have Influence on Oral Cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.737321728.793574925 ◽

2020 ◽

Author(s):

Michael Glogauer ◽

Abdelahhad Barbour

Keyword(s):

Oral Cancer ◽

Oral Microbiota

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Oral Microbiota Identifies Patients in Early Onset Rheumatoid Arthritis

Microorganisms ◽

10.3390/microorganisms9081657 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1657

Author(s):

Anders Esberg ◽

Linda Johansson ◽

Ingegerd Johansson ◽

Solbritt Rantapää Dahlqvist

Keyword(s):

Rheumatoid Arthritis ◽

Early Onset ◽

Amplicon Sequencing ◽

Oral Bacteria ◽

Oral Microbiome ◽

Rrna Gene ◽

Oral Microbiota ◽

Disease Manifestation ◽

Periodontal Status ◽

Quality Register

Rheumatoid arthritis (RA) is the most common autoimmune inflammatory disease, and single periodontitis-associated bacteria have been suggested in disease manifestation. Here, the oral microbiota was characterized in relation to the early onset of RA (eRA) taking periodontal status into consideration. 16S rRNA gene amplicon sequencing of saliva bacterial DNA from 61 eRA patients without disease-modifying anti-rheumatic drugs and 59 matched controls was performed. Taxonomic classification at 98.5% was conducted against the Human Oral Microbiome Database, microbiota functions were predicted using PICRUSt, and periodontal status linked from the Swedish quality register for clinically assessed caries and periodontitis. The participants were classified into three distinct microbiota-based cluster groups with cluster allocation differences by eRA status. Independently of periodontal status, eRA patients had enriched levels of Prevotella pleuritidis, Treponema denticola, Porphyromonas endodontalis and Filifactor alocis species and in the Porphyromonas and Fusobacterium genera and functions linked to ornithine metabolism, glucosylceramidase, beta-lactamase resistance, biphenyl degradation, fatty acid metabolism and 17-beta-estradiol-17-dehydrogenase metabolism. The results support a deviating oral microbiota composition already in eRA patients compared with healthy controls and highlight a panel of oral bacteria that may be useful in eRA risk assessment in both periodontally healthy and diseased persons.

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Pre and Probiotics Involved in the Modulation of Oral Bacterial Species: New Therapeutic Leads in Mental Disorders?

Microorganisms ◽

10.3390/microorganisms9071450 ◽

2021 ◽

Vol 9 (7) ◽

pp. 1450

Author(s):

Yoann Maitre ◽

Rachid Mahalli ◽

Pierre Micheneau ◽

Alexis Delpierre ◽

Marie Guerin ◽

...

Keyword(s):

Systematic Review ◽

Central Nervous System ◽

Nervous System ◽

Oral Health ◽

Mental Disorders ◽

Meta Analysis ◽

Bacterial Species ◽

Oral Microbiome ◽

Oral Microbiota ◽

Therapeutic Leads

This systematic review aims to identify probiotics and prebiotics for modulating oral bacterial species associated with mental disorders. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline, we search the electronic MEDLINE database published till January 2021 to identify the studies on probiotics and/or prebiotics for preventing and treating major oral dysbiosis that provokes mental disorders. The outcome of the search produces 374 records. After excluding non-relevant studies, 38 papers were included in the present review. While many studies suggest the potential effects of the oral microbiota on the biochemical signalling events between the oral microbiota and central nervous system, our review highlights the limited development concerning the use of prebiotics and/or probiotics in modulating oral dysbiosis potentially involved in the development of mental disorders. However, the collected studies confirm prebiotics and/or probiotics interest for a global or targeted modulation of the oral microbiome in preventing or treating mental disorders. These outcomes also offer exciting prospects for improving the oral health of people with mental disorders in the future.

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The influence of orthodontic fixed appliances on the oral microbiota: A systematic review

Dental Press Journal of Orthodontics ◽

10.1590/2176-9451.19.2.046-055.oar ◽

2014 ◽

Vol 19 (2) ◽

pp. 46-55 ◽

Cited By ~ 34

Author(s):

Amanda Osório Ayres de Freitas ◽

Mariana Marquezan ◽

Matilde da Cunha Gonçalves Nojima ◽

Daniela Sales Alviano ◽

Lucianne Cople Maia

Keyword(s):

Systematic Review ◽

Methodological Quality ◽

Data Extraction ◽

Scientific Evidence ◽

Statistical Treatment ◽

Fusobacterium Nucleatum ◽

Oral Microbiota ◽

Periodontal Pathogens ◽

Inclusion Criteria ◽

Fixed Appliances

Objective: To investigate whether there is scientific evidence to support the hypothesis that the presence of orthodontic fixed appliances influences the oral microbiota. Methods: The search for articles was conducted in PubMed; ISI Web of Knowledge and Ovid databases, including articles published in English until May 17th, 2012. They should report human observational studies presenting the following keywords: "fixed orthodontic appliance" AND "microbiological colonization"; OR "periodontal pathogens"; OR "Streptococcus"; OR "Lactobacillus"; OR "Candida"; OR "Tannerella forsythia"; OR "Treponema denticola"; OR "Fusobacterium nucleatum"; OR "Actimomyces actinomycetemcomitans"; OR "Prevotella intermedia", OR "Prevotella nigrescens"; OR "Porphyromonas gingivalis". Articles were previously selected by title and abstract. Articles that met the inclusion criteria were analyzed and classified as having low, moderate or high methodology quality. A new detailed checklist for quality assessment was developed based on the information required for applicable data extraction for reviews. The study design, sample, follow-up period, collection and microbial analysis methods, statistical treatment, results and discussion were assessed. Results: The initial search retrieved 305 articles of which 33 articles were selected by title and abstract. After full-text reading, 8 articles met the inclusion criteria, out of which 4 articles were classified as having low and 4 as moderate methodological quality. The moderate methodological quality studies were included in the systematic review. Conclusions: The literature revealed moderate evidence that the presence of fixed appliances influences the quantity and quality of oral microbiota.

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