As one of the most prevalent infective diseases worldwide, it is crucial that we not only know the constituents of the oral microbiome in dental caries but also understand its functionality. Herein, we present a reproducible meta‐analysis to effectively report the key components and the associated functional signature of the oral microbiome in dental caries. Publicly available sequencing data were downloaded from online repositories and subjected to a standardized analysis pipeline before analysis. Meta‐analyses identified significant differences in alpha and beta diversities of carious microbiomes when compared to healthy ones. Additionally, machine learning and receiver operator characteristic analysis showed an ability to discriminate between healthy and disease microbiomes. We identified from importance values, as derived from random forest analyses, a group of genera, notably containing Selenomonas, Aggregatibacter, Actinomyces and Treponema, which can be predictive of dental caries. Finally, we propose the most appropriate study design for investigating the microbiome of dental caries by synthesizing the studies, which had the most accurate differentiation based on random forest modelling. In conclusion, we have developed a non‐biased, reproducible pipeline, which can be applied to microbiome meta‐analyses of multiple diseases, but importantly we have derived from our meta‐analysis a key group of organisms that can be used to identify individuals at risk of developing dental caries based on oral microbiome inhabitants.
Bacterial vaginosis (BV) affects approximately 26% of women of childbearing age globally, presenting with 3-5 times increased risk of miscarriage and two-fold risk of pre-term birth. Antibiotics (metronidazole and clindamycin) are typically employed to treat BV; however the success rate is low due to the formation of recalcitrant polymicrobial biofilms. As a novel therapeutic, promising results have been obtained in vitro using Gardnerella endolysins, although to date their efficacy has only been demonstrated against simple biofilm models. In this study, a four-species biofilm was developed consisting of Gardnerella vaginalis, Fannyhessea vaginae, Prevotella bivia and Mobiluncus curtisii. Biofilms were grown in NYC III broth and treated using antibiotics and an anti-Gardnerella endolysin (CCB7.1) for 24 h. Biofilm composition, viability and structure were assessed using colony counts, live/dead qPCR and scanning electron microscopy. All species colonised biofilms to varying degrees, with G. vaginalis being the most abundant. Biofilm composition remained largely unchanged when challenged with escalated concentrations of conventional antibiotics. A Gardnerella-targeted endolysin candidate (CCB7.1) showed efficacy against several Gardnerella species planktonically, and significantly reduced viable G. vaginalis within polymicrobial biofilms at 1 to 4X pMIC (p < 0.05 vs. vehicle control). Collectively, this study highlights the resilience of biofilm-embedded pathogens against the currently used antibiotics and provides a polymicrobial model that allows for more effective pre-clinical screening of BV therapies. The Gardnerella-specific endolysin CCB7.1 demonstrated significant activity against G. vaginalis within polymicrobial biofilms, altering the overall community dynamic and composition.
Candida auris can persistently colonize human skin, alongside a diverse bacterial microbiome. In this study we aimed to investigate the efficacy of antiseptic activities on dual-species interkingdom biofilms containing staphylococci to determine if antiseptic tolerance was negatively impacted by dual-species biofilms. Chlorhexidine, povidone iodine, and hydrogen peroxide (H2O2), were able to significantly reduce biofilm viable cell counts following exposure at 2%, 10%, and 3%, respectively. Notably, H2O2-treated biofilms were able to significantly recover and considerably repopulate following treatment. Fortunately, inter-kingdom interactions in dual-species biofilms of C. auris and staphylococci did not increase the tolerance of C. auris against antiseptics in vitro. These data indicate mixed infections are manageable with chlorhexidine and povidone iodine, but caution should be exercised in the consideration of H2O2.
In recent years, high-throughput technologies have facilitated the widespread use of metabolomics to identify biomarkers and targets for oral squamous cell carcinoma (OSCC). As a result, the primary goal of this systematic review is to identify and evaluate metabolite biomarkers and their pathways for OSCC that featured consistently across studies despite methodological variations. Six electronic databases (Medline, Cochrane, Web of Science, CINAHL, ProQuest, and Embase) were reviewed for the longitudinal studies involving OSCC patients and metabolic marker analysis (in accordance with PRISMA 2020). The studies included ranged from the inception of metabolomics in OSCC (i.e., 1 January 2007) to 30 April 2023. The included studies were then assessed for their quality using the modified version of NIH quality assessment tool and QUADOMICS. Thirteen studies were included after screening 2285 studies. The majority of the studies were from South Asian regions, and metabolites were most frequently derived from saliva. Amino acids accounted for more than quarter of the detected metabolites, with glutamate and methionine being the most prominent. The top dysregulated metabolites indicated dysregulation of six significantly enriched pathways including aminoacyl-tRNA biosynthesis, glutathione metabolism and arginine biosynthesis with the false discovery rate (FDR) <0.05. Finally, this review highlights the potential of metabolomics for early diagnosis and therapeutic targeting of OSCC. However, larger studies and standardized protocols are needed to validate these findings and make them a clinical reality.
Endodontic infection is a biofilm disease that is difficult to irradicate with current treatment protocols, and as such, persistent micro-organisms may lead to ongoing or recurrent disease. The potential for the use of enhanced filling materials to modify biofilm regrowth is a promising strategy. This current study aimed to evaluate the anti-biofilm efficacy of calcium silicate cements modified with chitosan. The development of mono-species and multi-species biofilms on ProRoot MTA, Biodentine and bovine dentine discs were explored using quantitative microbiology analysis. The effect on regrowth of biofilms was assessed following the addition of chitosan to each cement. In comparison to a dentine substrate, both materials did not show the ability to inhibit biofilm regrowth. Biodentine incorporated with chitosan displayed a dose-dependent reduction in multi-species biofilm regrowth, unlike MTA. Notably, interkingdom biofilms were shown to enhance bacterial tolerance in the presence of chitosan. This study demonstrates the potential to enhance the antimicrobial properties of Biodentine. The findings highlight the need for appropriate model systems when exploring antimicrobial properties of materials in vitro so that interspecies and interkingdom interactions that modify tolerance are not overlooked while still supporting the development of innovative materials.