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Simple Summary The early detection of oral cancer is a high priority, as improvements in this area could lead to greater cure rates and reduced disability due to extensive surgery. Oral cancer is very difficult to detect in over 70% of cases as it develops unseen until quite advanced, sometimes rapidly. Therefore, the development of markers in body fluids (liquid biopsies) indicative of cancerous changes have a high priority. We show here that small molecules called metabolites can distinguish between non-diseased oral cells and two types of cells found in oral cells on the road to cancer. Although our investigation is preliminary, some of the metabolites have already been detected in the saliva (split) of oral cancer patients, and could eventually help detect oral cancer development at an earlier stage. Abstract Premalignant oral lesions (PPOLs) which bypass senescence (IPPOL) have a much greater probability of progressing to malignancy, but pre-cancerous fields also contain mortal PPOL keratinocytes (MPPOL) that possess tumour-promoting properties. To identify metabolites that could potentially separate IPPOL, MPPOL and normal oral keratinocytes non-invasively in vivo, we conducted an unbiased screen of their conditioned medium. MPPOL keratinocytes showed elevated levels of branch-chain amino acid, lipid, prostaglandin, and glutathione metabolites, some of which could potentially be converted into volatile compounds by oral bacteria and detected in breath analysis. Extracellular metabolites were generally depleted in IPPOL, and only six were elevated, but some metabolites distinguishing IPPOL from MPPOL have been associated with progression to oral squamous cell carcinoma (OSCC) in vivo. One of the metabolites elevated in IPPOL relative to the other groups, citrate, was confirmed by targeted metabolomics and, interestingly, has been implicated in cancer growth and metastasis. Although our investigation is preliminary, some of the metabolites described here are detectable in the saliva of oral cancer patients, albeit at a more advanced stage, and could eventually help detect oral cancer development earlier.

Background and ObjectiveOral malodour is often observed in gingivitis and chronic periodontitis patients, and the tongue microbiota is thought to play a major role in malodorous gas production, including Volatile Sulfur Compounds (VSCs) such as hydrogen sulfide (H2S) and methanethiol (CH3SH). This study aimed to examine the link between the presence of VSCs in mouth air (as a marker of oral malodour) and the oral bacterial ecology in the tongue and periodontal niches of healthy, gingivitis and periodontitis patients.MethodsParticipants were clinically assessed using plaque index, bleeding on probing (BOP) and periodontal probing depths, and VSC concentrations in their oral cavity measured using a portable gas chromatograph. Tongue scrapings, subgingival and interdental plaque were collected from healthy individuals (n=22), and those with gingivitis (n=14) or chronic periodontitis (n=15). The bacterial 16S rRNA gene region V3-V4 in these samples was sequenced and the sequences analysed using the Minimum Entropy Decomposition pipeline.ResultsElevated VSC concentrations and CH3SH:H2S were observed in periodontitis compared to health. Significant ecological differences were observed in the tongue microbiota of healthy subjects with high plaque scores compared to low plaque scores, suggesting a possible connection between the microbiota of the tongue and the periodontium and that key dysbiotic changes may be initiated in the clinically healthy who have higher dental plaque accumulation. Greater subgingival bacterial diversity was positively associated with H2S in mouth air. Periodontopathic bacteria known to be prolific VSC producers increased in abundance on the tongue associated with increased bleeding on probing (BOP) and total percentage of periodontal pockets >6mm, supporting the suggestion that the tongue may become a reservoir for periodontopathogens.ConclusionThis study highlights the importance of the periodontal microbiota in malodour and has detected dysbiotic changes in the tongue microbiota in periodontitis.

Wound bioburden plays an important role in impaired healing and development of infection-related complications. The objective of this study was to determine the efficacy of an innovative two-layer nitric oxide-generating system (NOx) to prevent and treat biofilms formed by bacterial and fungal pathogens commonly associated with wound infection, and activity against Pseudomonas aeruginosa virulence factors. Single- and mixed-species biofilms were grown for 24 h on nitrocellulose filters placed on agar. Filters were covered with either NOx or placebo, before and after biofilm formation. Populations of bacteria and yeasts were determined using viable counts. Pyocyanin and elastase production from P. aeruginosa were determined in supernatants derived from suspended biofilms. Efficacy of NOx was demonstrated against Staphylococcus aureus, P. aeruginosa, Acinetobacter baumannii, Escherichia coli and Candida spp. Population reductions between 2- and 10-log fold were observed. Pyocyanin and elastase activities from P. aeruginosa were reduced 1.9- and 3.2-fold, respectively. This study demonstrated activity of NOx against formation and treatment of single- and mixed-species biofilms, including multidrug-resistant strains. NOx represents a new generation of antimicrobial agent with potent, broad-spectrum activity, and with no evidence of resistance development.

Purpose of Review The purpose of this study is to critically assess recent studies concerning the use of probiotics to control periodontal diseases, dental caries and halitosis (oral malodour). Recent Findings Clinical studies have shown that probiotics when allied to conventional periodontal treatment can ameliorate microbial dysbiosis and produce significant improvement in clinical indicators of disease. However, this effect is often not maintained by the host after the end of probiotic use. Current probiotics also show limited effects in treating caries and halitosis. Novel approaches based up on replacement therapy and using highly abundant health-associated oral species, including nitrate-reducing bacteria, have been proposed to improve persistence of probiotic strains and maintain oral health benefits. Summary Probiotics have potential in the management of multifactorial diseases such as the periodontal diseases and caries, by more effectively addressing the host-microbial interface to restore homeostasis that may not be achieved with conventional treatments.