ObjectiveThis study aimed to determine if the oral potentially malignant disorder, oral leukoplakia (OLK), exhibited microbiome changes that predict the degree of dysplasia and the risk of malignant progression.ResultsWe examined the microbiome in 216 swabs of OLK from 177 patients. Compared to healthy controls (n = 120 swabs from 61 patients), who were less likely to smoke and had better oral health, OLK patients exhibited an increased abundance of Rothia mucilaginosa, Streptococcus parasanguinis and S. salivarius, resembling acetaldehyde generating communities described previously. Compared to the patients' healthy contralateral normal (CLN) mucosa (n = 202), which acts as a matched control for oral health parameters, OLK exhibited increased S. infantis, Leptotrichia spp., Bergeyella spp., Porphyromonas spp. and F. nucleatum. Machine learning with clinical and microbiome data could discriminate high-risk dysplasia (moderate to severe) from low-risk dysplasia (none or mild) (sensitivity 87.4%; specificity 76.5%). Follow-up swabs were recovered from 58 patients, eight of whom progressed to a higher grade of dysplasia or OSCC and these eight patients exhibited a higher abundance of Fusobacterium species at their initial presentation.ConclusionsOur study suggests that the OLK microbiome has potential to be an aid to the prediction of dysplasia grade and the risk of malignant transformation.

Candida albicans is an opportunistic fungal pathogen associated with superficial and systemic infections in humans. Azole antifungal resistance in C. albicans is of clinical concern, and both oral and systemic Candida infections can be difficult to treat due to the lack of alternative antifungal drugs. Expression of a hyperactive form of the transcription factor Tac1 is a major contributor to azole resistance in C. albicans isolates resulting in the increased expression of the azole efflux pump Cdr1. In this study, we investigated whether the Mediator tail component Med2, encoded by the expanded (n=14) TLO gene family of C. albicans, was required for Tac1 activity. A homozygous TAC1-5 gain-of-function point mutation was introduced into WT, tloΔ and med3Δ strains of C. albicans which enables them to express hyperactive Tac1. qRT-PCR analysis revealed that tloΔ-TAC1-5 had reduced basal and fluphenazine-induced CDR1 expression relative to WT-TAC1-5 strains and exhibited reduced levels of resistance to fluconazole and terbinafine. Individual copies of representatives from each of the alpha, beta and gamma TLO clades were reintroduced into tloΔ-TAC1-5 to investigate their ability to restore Tac1-activated resistance. These studies show that alpha and beta TLO genes could restore fluconazole resistance in the tloΔ-TAC1-5 background, whereas gamma clade genes did not result in any detectable phenotypic complementation. Transcript profiling showed that reintroduction of TLOα1 led to increased expression of TAC1-5-activated genes such as CDR1. Further analysis using ChIP-qPCR revealed that Tloα1 localizes to the drug response element which is the site where Tac1 binds to the CDR1 promoter. These data have identified that the TLO gene family is required for the expression of Tac1-mediated fluconazole resistance. However, this effect is confined to members of the alpha and beta, but not the gamma, TLO clades.

INTRODUCTION:Pneumonia is a leading cause of death for people with intellectual and developmental disabilities (IDD), who also have increased risk of oral disease. Given the known relationship between oral disease and pneumonia in similar populations, this review aims to explore what is known about the association between oral health and pneumonia among people with IDD. METHODS:This systematic scoping review was carried out in accordance with the Joanna Briggs Institute methods and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist (PRISMA-ScR). A systematic search of Medline (Ovid), Embase, Cochrane Trials, Cochrane Review, CINAHL and PubMed was conducted, guided by a registered protocol. The PCC framework informed the search and inclusion criteria. Titles and abstracts were independently screened by two reviewers, with full texts assessed for relevance to oral health and pneumonia in adults with IDD. RESULTS:Following a protocol and defined criteria, (2544) articles were abstract screened; a further (31) reached full-text review, with (7) included in this review. Study designs included cross-sectional studies (2), retrospective cohorts (2), prospective cohorts (2) and one RCT pilot (1). Six studies reported oral carriage of respiratory pathogens such as Streptococcus pneumoniae, Pseudomonas aeruginosa and Klebsiella pneumoniae. Two studies reported predictive relationships between oral pathogens and pneumonia, with increased odds of respiratory illness associated with positive PCR results for specific pathogens (OR 9.0, 95% confidence interval [CI] 2.3-38.8). Two studies identified poor oral health as a predictor of pneumonia, using validated tools such as the ROAG (OR 1.6, 95% CI 1.1-2.5). Mediating factors included enteral feeding, level of IDD, and history of oral disease. CONCLUSIONS:Research consistently finds carriage of potential respiratory pathogens in the oral microbiome of people with IDD. Despite this, there is a significant lack of research into the relationship between the oral microbiome, poor oral health, and pneumonia in this population, though the latter two are both prevalent and consequential. There is an urgent need for further research exploring the role that oral health and the oral microbiome play in pneumonia among people with IDD.

Introduction:Mounting evidence links F. nucleatum, particularly subsp. polymorphum (now classified as F. polymorphum) to oral squamous cell carcinoma (OSCC). However, not all studies support this association, and its ubiquitous presence in health complicates its role as a driver of disease, raising a fundamental question: Can some isolates be pathogenic "high risk" while others are not? Here, we investigated the carcinogenic potential of clinical isolates of F. polymorphum from oral dysplastic lesions. Methods:Sixteen, fully sequenced F. polymorphum isolates from healthy subjects (6 isolates) or patients with mild epithelial dysplasia (3 isolates), moderate dysplasia (3 isolates) or severe dysplasia/OSCC (4 isolates) were included. The isolates were assessed for their effect on the proliferation, migration, invasion, transcriptome and cytokinome of dysplastic oral keratinocytes (DOK). The isolates were also subject to RNA-seq and secreted amyloid FadA analyses. Results:Although genetically indistinguishable, the isolates differed markedly in their effects on dysplastic oral keratinocytes (DOK) with isolates from dysplastic lesions demonstrating enhanced proliferation, migration, and invasion of DOK in proportion to the dysplasia severity of their clinical origin. Strikingly, amyloid-like FadA levels were also significantly higher in dysplasia-associated "high-risk" isolates and correlated with their pro-carcinogenic effects. RNA-seq further showed upregulation of heme acquisition genes in high risk isolates. Transcriptome and cytokine profiling of DOK revealed a uniform pro-inflammatory response across all isolates, independent of origin, but genes and pathways related to proliferation correlated with dysplasia severity. Supporting this, 45% of the most severity-correlated host genes identified in vitro were also differentially expressed in the same direction in tumors versus normal tissues in the TCGA OSCC dataset. Conclusion:These results show, for the first time, that clinical oral isolates of F. polymorphum vary in their carcinogenic properties, establishing the novel concept of "high-risk" versus "low-risk" isolates in oral carcinogenesis, potentially driven by genome-independent regulation.

Objectives This study aimed to assess (i) awareness of the signs and symptoms of oral cancer and its risk factors and (ii) awareness and attitudes towards oral cancer screening, in an Irish cohort. Methods A cross-sectional self-administered survey was used in a convenience sample of patients > 18 years with no cancer history attending the Dublin Dental University Hospital. The data were analysed using descriptive statistics, Pearson’s Chi-squared and Fisher’s exact tests. Results 124 responses were received. 83.7% reported knowing little/nothing about oral cancer risk factors. 12.8% did not identify smoking, 35.3% alcohol consumption, 90.5% betel nut, 35.3% age and 80.2% male gender, as risk factors. 46% were unaware that a dentist is trained to check for oral cancer. Participants were more likely to seek advice regarding a persistent oral white or red patch from their doctor than their dentist but were more likely to attend their dentist in relation to a persistent ulcer, swelling or pain. The study did not find any statistically significant relationship between gender, age, educational level and either awareness of the signs and symptoms of oral cancer and its risk factors, or with experiences and attitudes towards oral cancer screening. Conclusions The study demonstrated a lack of knowledge of the risk factors, signs and symptoms of oral cancer, and of awareness of the role of dentists in screening for oral cancer. It should be repeated in a larger cohort in non-dental settings to inform the development of oral cancer awareness programmes that address those areas where awareness is lacking.

Development of resistance and tolerance to antifungal drugs in Candida albicans can compromise treatment of infections caused by this pathogenic yeast species. The uniquely expanded C. albicans TLO gene family is comprised of 14 paralogous genes which encode Med2, a subunit of the multiprotein Mediator complex which is involved in the global control of transcription. This study investigates the acquisition of fluconazole tolerance in a mutant in which the entire TLO gene family has been deleted. This phenotype was reversed to varying degrees upon reintroduction of representative members of the alpha- and beta-TLO clades (i.e. TLO1 and TLO2), but not by TLO11, a gamma-clade representative. Comparative RNA sequencing analysis revealed changes in the expression of genes involved in a range of cellular functions, including ergosterol biosynthesis, mitochondrial function, and redox homeostasis. This was supported by the results of mass spectrometry analysis, which revealed alterations in sterol composition of the mutant cell membrane. Our data suggest that members of the C. albicans TLO gene family are involved in the control of ergosterol biosynthesis and mitochondrial function and may play a role in the responses of C. albicans to azole antifungal agents.

Fusobacterium nucleatum is an anaerobic commensal of the oral cavity associated with periodontitis and extra-oral diseases, including colorectal cancer. Previous studies have shown an increased relative abundance of this bacterium associated with oral dysplasia or within oral tumours. Using direct culture, we found that 75 % of Fusobacterium species isolated from malignant or potentially malignant oral mucosa were F. nucleatum subsp. polymorphum. Whole genome sequencing and pangenome analysis with Panaroo was carried out on 76 F. nucleatum subsp. polymorphum genomes. F. nucleatum subsp. polymorphum was shown to possesses a relatively small core genome of 1604 genes in a pangenome of 7363 genes. Phylogenetic analysis based on the core genome shows the isolates can be separated into three main clades with no obvious genotypic associations with disease. Isolates recovered from healthy and diseased sites in the same patient are generally highly related. A large repertoire of adhesins belonging to the type V secretion system (TVSS) could be identified with major variation in repertoire and copy number between strains. Analysis of intergenic recombination using fastGEAR showed that adhesin complement is shaped by horizontal gene transfer and recombination. Recombination events at TVSS adhesin genes were not only common between lineages of subspecies polymorphum, but also between different subspecies of F. nucleatum. Strains of subspecies polymorphum with low copy numbers of TVSS adhesin encoding genes tended to have the weakest adhesion to oral keratinocytes. This study highlights the genetic heterogeneity of F. nucleatum subsp. polymorphum and provides a new framework for defining virulence in this organism.

Fusobacterium nucleatum is an anaerobic commensal of the oral cavity recently reported to be associated with cancers of the gastrointestinal tract and oral squamous cell carcinoma (OSCC). In this study, we investigate the impact on oral keratinocytes of infection with a genetically diverse set of strains of F. nucleatum subsp. polymorphum recovered from patients with oral dysplasia (n=6). We employed H357 oral keratinocytes derived from a stage 1 OSCC and H376 cells derived from a stage 3 OSCC. Adhesion phenotypes were strain specific, with 3/6 clinical isolates examined exhibiting higher adherence to the stage 3 H376 cell line. Conversely, intracellular invasion was greatest in the H357 cells and was associated with specific transcriptional responses including autophagy and keratinization. Infection of both H357 and H376 cell lines induced transcriptional and cytokine responses linked to cancer cell migration and angiogenesis. F. nucleatum infection induced greater levels of MMP9 secretion in the H376 cell line which was associated with enhanced motility and invasion phenotypes. Additionally, the degree of F. nucleatum induced invasive growth by H376 cells varied between different clinical isolates of F. nucleatum subsp. polymorphum. Blockage of CCL5 signalling using the inhibitor metCCL5 resulted in reduced keratinocyte invasion. F. nucleatum infection also induced expression of the pro-angiogenic chemokine MCP-1 and the angiogenic growth factor VEGF-A resulting in increased capillary-like tube formation in HUVEC cells, most significantly in H376 cells. Treatment of HUVEC cells with resveratrol, a VEGF-A signalling inhibitor, significantly attenuated F. nucleatum induced tube formation. Our data indicate that the outcomes of F. nucleatum-oral cell interactions can vary greatly depending on the bacterial genotype and the malignant phenotype of the host cell.

The tongue and floor of the mouth are high-risk sites for oral squamous cell carcinoma (OSCC), while smoking is its most significant risk factor. Recently, questions have been raised as to the role of the oral microbiome in OSCC because of a wealth of evidence demonstrating that the microbiome of OSCC differs from that of healthy mucosa. However, oral site and smoking also have a significant impact on oral microbial communities, and to date, the role these factors play in influencing the dysbiotic microbial communities of OSCC and precursor lesions has not been considered. This review aims to examine the influence of site and smoking on the oral microbiome and, in turn, whether these microbiome changes could be involved in oral carcinogenesis.

We investigated bacterial colonisation patterns of healthy mucosa (buccal, tongue, palate and floor of mouth) in a cohort of adults in order to determine how smoking, tooth loss, plaque levels and oral hygiene practices impacted on mucosal colonisation. A total of 322 swabs were recovered from 256 participants, of whom 46% were current smokers. We analysed colonization by sequencing the V1-V3 regions of the 16S rRNA gene. Palate and tongue microbiomes generally exhibited greater biodiversity than buccal and floor of mouth. Although Neisseria, Lautropia and Haemophilus spp. showed reduced abundance in smokers, buccal mucosa specifically showed a significant increase in Prevotella spp., whereas tongue and floor of mouth tended towards increased abundance of Streptococcus spp. Unexpectedly, tooth brushing frequency had a greater impact on mucosal community structure than plaque levels. Tooth loss was associated with significant reductions in mucosal biodiversity and had site-specific impacts, with buccal communities showing increased abundance of periodontitis-associated species and Rothia mucilaginosa, whereas tongue communities exhibited increased abundance of several streptococcal OTUs and reduced abundance of Haemophilus spp. This study highlights the complex relationship between mucosal colonisation and host factors, highlighting the need for careful consideration of these factors in mucosal microbiome studies.

Human saliva contains natural antimicrobial enzymes. In this in-vitro study, we evaluate the antimicrobial activity of a dentifrice containing a salivary enzyme complex (SEC) with xylitol versus a standard 0.12% chlorhexidine (CHX) dentifrice. Adherent cells of Streptococcus gordonii, Strep. mutans, Actinomyces naeslundii, Fusobacterium nucleatum subsp polymorphum, and Corynebacterium matruchotii were exposed to SEC-xylitol and CHX dentifrices for 2 min and viable CFUs were enumerated. Exposure to the SEC-xylitol dentifrice resulted in a significant reduction in bacterial viability, which was greater than that shown by the CHX dentifrice, against all organisms tested. The SEC-xylitol dentifrice also exhibited greater antimicrobial activity against all organsims in well diffusion assays compared to CHX. Dentifrice activity was also evaluated against a three species community of Strep. gordonii, Strep. mutans, and Coryne. matruchotii using bacterial live/dead stain. The SEC-xylitol dentifrice was at least as effective as CHX in removal of the multispecies community. The combination of SEC and xylitol generates a highly effective antimicrobial dentifrice with greater antibacterial activity than a standard 0.12% CHX formulations. SEC and xylitol combinations are worthy of further investigation for routine use and in the management of gingivitis and periodontal disease.

AIM:To investigate whether there is an association between subgingival microbial diversity and reduced respiratory function. MATERIALS AND METHODS:A group of dentate 58-72-year-old men in Northern Ireland had a comprehensive periodontal examination including subgingival plaque sampling. DNA was extracted from plaque samples and the V1-V3 regions of the 16S rRNA gene were analysed by high-throughput sequencing and a microbial diversity index (MDI) was derived. Spirometry measurements were made using a wedge bellows spirometer. The primary outcome variable of interest was the percentage of predicted forced expiratory volume in 1 s (% predicted FEV1 ). Analysis included multiple linear regression with adjustment for various confounders. RESULTS:Five-hundred and seven men were included in the analysis. The mean age was 63.6 years (SD = 3.1). Of these, 304 (60.0%) men had no or mild periodontitis, 105 (20.7%) had moderate periodontitis and 98 (19.3%) had severe periodontitis. Multiple linear regression analysis showed that a one unit increase in MDI was associated with a 0.71% loss (95% confidence interval: 0.06%-1.35%; p = .03) in % predicted FEV1 after adjustment for all confounders. CONCLUSIONS:In this group of dentate men from Northern Ireland, subgingival microbial diversity was associated with reduced respiratory function.

The Candida albicans genome contains between ten and fifteen distinct TLO genes that all encode a Med2 subunit of Mediator. In order to investigate the biological role of Med2/Tlo in C. albicans we deleted all fourteen TLO genes using CRISPR-Cas9 mutagenesis. ChIP-seq analysis showed that RNAP II localized to 55% fewer genes in the tloΔ mutant strain compared to the parent, while RNA-seq analysis showed that the tloΔ mutant exhibited differential expression of genes required for carbohydrate metabolism, stress responses, white-opaque switching and filamentous growth. Consequently, the tloΔ mutant grows poorly in glucose- and galactose-containing media, is unable to grow as true hyphae, is more sensitive to oxidative stress and is less virulent in the wax worm infection model. Reintegration of genes representative of the α-, β- and γ-TLO clades resulted in the complementation of the mutant phenotypes, but to different degrees. TLOα1 could restore phenotypes and gene expression patterns similar to wild-type and was the strongest activator of glycolytic and Tye7-regulated gene expression. In contrast, the two γ-TLO genes examined (i.e., TLOγ5 and TLOγ11) had a far lower impact on complementing phenotypic and transcriptomic changes. Uniquely, expression of TLOβ2 in the tloΔ mutant stimulated filamentous growth in YEPD medium and this phenotype was enhanced when Tloβ2 expression was increased to levels far in excess of Med3. In contrast, expression of reintegrated TLO genes in a tloΔ/med3Δ double mutant background failed to restore any of the phenotypes tested, suggesting that complementation of these Tlo-regulated processes requires a functional Mediator tail module. Together, these data confirm the importance of Med2/Tlo in a wide range of C. albicans cellular activities and demonstrate functional diversity within the gene family which may contribute to the success of this yeast as a coloniser and pathogen of humans.

Fluoride is added to drinking water in some countries to prevent tooth decay (caries). There is no conclusive evidence that community water fluoridation (CWF) at WHO recommended concentrations for caries prevention has any harmful effects. However, research is ongoing regarding potential effects of ingested fluoride on human neurodevelopment and endocrine dysfunction. Simultaneously, research has emerged highlighting the significance of the human microbiome in gastrointestinal and immune health. In this review we evaluate the literature examining the effect of fluoride exposure on the human microbiome. Unfortunately, none of the studies retrieved examined the effects of ingested fluoridated water on the human microbiome. Animal studies generally examined acute fluoride toxicity following ingestion of fluoridated food and water and conclude that fluoride exposure can detrimentally perturb the normal microbiome. These data are difficult to extrapolate to physiologically relevant human exposure dose ranges and the significance to humans living in areas with CWF requires further investigation. Conversely, evidence suggests that the use of fluoride containing oral hygiene products may have beneficial effects on the oral microbiome regarding caries prevention. Overall, while fluoride exposure does appear to impact the human and animal microbiome, the long-term consequences of this requires further study.

Human saliva contains natural antimicrobial enzymes. In this in-vitro study, we evaluate the antimicrobial activity of a dentifrice containing a salivary enzyme complex (SEC) with xylitol versus a standard 0.12% chlorhexidine (CHX) dentifrice. Adherent cells of Streptococcus gordonii, Strep. mutans, Actinomyces naeslundii, Fusobacterium nucleatum subsp polymorphum, and Corynebacterium matruchotii were exposed to SEC-xylitol and CHX dentifrices for 2 min and viable CFUs were enumerated. Exposure to the SEC-xylitol dentifrice resulted in a significant reduction in bacterial viability, which was greater than that shown by the CHX dentifrice, against all organisms tested. The SEC-xylitol dentifrice also exhibited greater antimicrobial activity against all organsims in well diffusion assays compared to CHX. Dentifrice activity was also evaluated against a three species community of Strep. gordonii, Strep. mutans, and Coryne. matruchotii using bacterial live/dead stain. The SEC-xylitol dentifrice was at least as effective as CHX in removal of the multispecies community. The combination of SEC and xylitol generates a highly effective antimicrobial dentifrice with greater antibacterial activity than a standard 0.12% CHX formulations. SEC and xylitol combinations are worthy of further investigation for routine use and in the management of gingivitis and periodontal disease.

Whether to commit limited cellular resources toward growth and proliferation, or toward survival and stress responses, is an essential determination made by Target of Rapamycin Complex 1 (TORC1) for a eukaryotic cell in response to favorable or adverse conditions. Loss of TORC1 function is lethal. The TORC1 inhibitor rapamycin that targets the highly conserved Tor kinase domain kills fungal pathogens like Candida albicans , but is also severely toxic to human cells. The least conserved region of fungal and human Tor kinases are the N-terminal HEAT domains. We examined the role of the 8 most N-terminal HEAT repeats of C . albicans Tor1. We compared nutritional- and stress responses of cells that express a message for N-terminally truncated Tor1 from repressible tetO , with cells expressing wild type TOR1 from tetO or from the native promoter. Some but not all stress responses were significantly impaired by loss of Tor1 N-terminal HEAT repeats, including those to oxidative-, cell wall-, and heat stress; in contrast, plasma membrane stress and antifungal agents that disrupt plasma membrane function were tolerated by cells lacking this Tor1 region. Translation was inappropriately upregulated during oxidative stress in cells lacking N-terminal Tor1 HEAT repeats despite simultaneously elevated Gcn2 activity, while activation of the oxidative stress response MAP kinase Hog1 was weak. Conversely, these cells were unable to take advantage of favorable nutritional conditions by accelerating their growth. Consuming oxygen more slowly than cells containing wild type TOR1 alleles during growth in glucose, cells lacking N-terminal Tor1 HEAT repeats additionally were incapable of utilizing non-fermentable carbon sources. They were also hypersensitive to inhibitors of specific complexes within the respiratory electron transport chain, suggesting that inefficient ATP generation and a resulting dearth of nucleotide sugar building blocks for cell wall polysaccharides causes cell wall integrity defects in these mutants. Genome-wide expression analysis of cells lacking N-terminal HEAT repeats showed dysregulation of carbon metabolism, cell wall biosynthetic enzymes, translational machinery biosynthesis, oxidative stress responses, and hyphal- as well as white-opaque cell type-associated genes. Targeting fungal-specific Tor1 N-terminal HEAT repeats with small molecules might selectively abrogate fungal viability, especially when during infection multiple stresses are imposed by the host immune system.

Background: There is a limited literature describing the oral microbiome and its diagnostic potential in paediatric inflammatory bowel disease [IBD]. Methods: We examined the dorsum tongue microbiome by V1-V2 sequencing in a cohort of 156 treatment-naive children diagnosed with IBD compared to 102 healthy control children. Microbiome changes over time following treatment were examined in a subset of patients and associations between IBD diagnosis and dysbiosis were explored. Results: Analysis of community structure of the microbiome in tongue samples revealed that IBD samples diverged significantly from healthy control samples [PERMANOVA p = 0.0009] and exhibited a reduced abundance of Clostridia in addition to several major oral genera [Veillonella, Prevotella and Fusobacterium species] with an increased abundance of streptococci. This dysbiosis was more marked in patients with severe disease. Higher levels of the potential pathobionts Klebsiella and Pseudomonas spp. were also associated with IBD. In terms of predicted functions, the IBD oral microbiome was potentially more acidogenic and exhibited reduced capacity for B vitamin biosynthesis. We used a machine learning approach to develop a predictive model of IBD which exhibited a mean-prediction AUC [area under the ROC curve] of 0.762. Finally, we examined a subset of 53 patients following 12 months of therapy and could show resolution of oral dysbiosis as demonstrated by a shift towards a healthy community structure and a significant reduction in oral dysbiosis. Conclusion: Oral dysbiosis found in children with IBD is related to disease severity and resolves over time following successful IBD treatment.

Candida albicans has between 10-15 Telomere-associated ORF family(TLO)genes, whereas its closest relative, Candida dubliniensis, has two. The Tlo proteins are components of the Mediator complex which plays an important role in transcriptional regulation. CRISPR-Cas9 mutagenesis was used to generate a TLOnull mutant of C. albicans. Phenotypic analysis of the mutant showed significantly reduced fitness, with major defects in growth rate, morphogenesis, stress resistance and virulence in a Galleria mellonellamodel. Clade representative TLOα1, TLOβ2 and TLOγ11constructs were reintroduced into the null mutant background to determine if members of the TLO gene family exhibit functional differences. The genes were reintroduced under the control of the TET1 and ENO1promoters. TLOα1and TLOβ2expression restored stress tolerance and growth rate, in some cases to the level of the WT. TLOβ2expression also showed a dramatic effect on morphology resulting in constitutive true hyphal growth. Moderate expression of TLOγ11 had no detectable effect on many of the phenotypes tested, however overexpression increased biofilm formation in Spider medium, and also conferred increased resistance to cell wall stressors. These data suggest that individual TLO genes have distinct functions and that the diversity within the TLO family may contribute to the relative success of C. albicans as a coloniser and pathogen of humans.

The oral cavity is continuous with the gastrointestinal tract and in children, oral health may be closely linked with the overall health of the GI tract. In the case of pediatric Crohn's disease (CD), oral manifestations are an important clinical indicator of intestinal disease. Recent studies of the microbiome in IBD suggest that translocation of oral microbes to the gut may be a common feature of the microbial dysbiosis which is a signature of both CD and ulcerative colitis (UC). Murine studies suggest that translocation of oral bacteria and yeasts to the lower GI tract may trigger inflammation in susceptible hosts, providing a mechanistic link to the development of IBD. Conversely, some studies have shown that dysbiosis of the oral microbiome may occur, possibly as a result of inflammatory responses and could represent a useful source of biomarkers of GI health. This review summarizes our current knowledge of the oral microbiome in IBD and presents current hypotheses on the potential role of this community in the pathogenesis of these diseases.