ObjectivesThe composition of dental plaque has been well defined, whereas currently there is limited understanding of the composition of denture plaque and how it directly influences denture related stomatitis (DS). The aims of this study were to compare the microbiomes of denture wearers, and to understand the implications of these towards inter-kingdom and host-pathogen interactions within the oral cavity.MethodsSwab samples were obtained from 123 participants wearing either a complete or partial denture; the bacterial composition of each sample was determined using bar-coded illumina MiSeq sequencing of the bacterial hypervariable V4 region of 16S rDNA. Sequencing data processing was undertaken using QIIME, clustered in Operational Taxonomic Units (OTUs) and assigned to taxonomy. The dentures were sonicated to remove the microbial flora residing on the prosthesis, sonicate was then cultured using diagnostic colorex Candida media. Samples of unstimulated saliva were obtained and antimicrobial peptides (AMP) levels were measured by ELISA.ResultsWe have shown that dental and denture plaques are significantly distinct both in composition and diversity and that the oral microbiome composition of a denture wearer is variable and is influenced by the location within the mouth. Dentures and mucosa were predominantly made up of Bacilli and Actinobacteria. Moreover, the presence of natural teeth has a significant impact on the overall microbial composition, when compared to the fully edentulous. Furthermore, increasing levels of Candida spp. positively correlate with Lactobacillus spp. AMPs were quantified, though showed no specific correlations.ConclusionsThis is the first study to provide a detailed understanding of the oral microbiome of denture wearers and has provided evidence that DS development is more complex than simply a candidal infection. Both fungal and bacterial kingdoms clearly play a role in defining the progression of DS, though we were unable to show a defined role for AMPs.

The role of polymicrobial biofilm infections in medicine is becoming more apparent. Increasing number of microbiome studies and deep sequencing has enabled us to develop a greater understanding of how positive and negative microbial interactions influence disease outcomes. An environment where this is particularly pertinent is within the oral cavity, a rich and diverse ecosystem inhabited by both bacteria and yeasts, which collectively occupy and coexist within various niches as biofilm communities. Studies within this environment have however tended to be subject to extensive independent investigation, in the context of either polymicrobial bacterial communities or yeast biofilms, but rarely both together. It is clear however that they are not mutually exclusive. Therefore, this review aims to explore the influence of candidal populations on the composition of these complex aggregates and biofilm communities, to investigate their mechanistic interactions to understand how these impact clinical outcomes, and determine whether we can translate how this knowledge can be used to improve patient management.

Cytokines mediate the balance between protective and destructive immunity in periodontitis. We sought to investigate the role of IL-33 in periodontitis. The expression of IL-33 in gingival tissue from healthy controls (n = 10) and patients with chronic periodontitis (n = 17) was investigated. Based on a murine model of periodontal disease, the function of IL-33 was determined first by administration of exogenous IL-33 and second by inhibition of IL-33 signaling using mice deficient in the IL-33 receptor ST2. Alveolar bone level, serum antibody, and lymphocyte responses were assessed in the murine model. Expression of IL-33 and ST2 was elevated in gingival tissues from patients with chronic periodontitis as compared with healthy tissues (P < 0.05). Similarly, Il33 expression was higher in periodontal tissues of Porphyromonas gingivalis-infected mice as compared with sham-infected controls (P < 0.05). IL-33 treatment of P. gingivalis-infected mice significantly exacerbated alveolar bone loss when compared with infection or IL-33 treatment alone (P < 0.001). Conversely, P. gingivalis infection-induced alveolar bone loss was attenuated in mice lacking ST2. The percentages of T and B lymphocytes expressing nuclear factor κB ligand (RANKL) in the gingival tissues and T lymphocytes expressing RANKL in the cervical draining lymph nodes were higher in IL-33-treated P. gingivalis-infected mice versus phosphate buffered saline-treated P. gingivalis-infected controls (all P < 0.001). Targeting the RANKL pathway by osteoprotegerin administration abrogated periodontal bone destruction in P. gingivalis-infected, IL-33-treated mice. These data demonstrate a previously unrecognized role for IL-33 in exacerbating bone loss in a RANKL-dependent manner in the context of bacterial infection and suggest that this pathway may be amenable to manipulation as a novel therapeutic target in periodontitis.

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The microbial plaque biofilm resides adjacent to the tissue-destructive inflammatory infiltrate in periodontitis. Although not sufficient, this biofilm is necessary for this inflammatory response. Patients with periodontitis generate antibodies specific for bacteria in the biofilm - although the role of these antibodies is not clear, there is, undoubtedly, an adaptive immune response in periodontitis. T lymphocytes are central to adaptive immunity, and provide help for B cells to generate specific antibodies. T-cell receptor recognition of peptide antigen in the context of major histocompatibility complex can result in T-cell activation. The activation and differentiation of the T-cell can take many forms, and hence numerous types of T cells have been described. The role of adaptive immune responses, and the T-cell component thereof, in periodontitis remains relatively poorly defined. This review aims to broadly summarize findings about T cells and their role in periodontitis, focusing primarily on studies of human disease with a short discussion of some animal studies.