Novel strategies to promote oral health

Project leader: Prof Bart Keijser
Time frame 2012 – 2016
Project code: OH001

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This project aimed to identify the biological processes in the oral ecosystem responsible for maintaining oral health. It was based on the hypothesis that ‘oral health’ is the ability of the oral ecosystem to adapt to and counteract stresses, where the oral ecosystem is defined as the tripartite of oral microbiota, saliva and host (mucosal) immunity. The project comprised five interconnected work packages; a sixth work package was focused on knowledge dissemination. WP1 aimed to provide a detailed description of the oral ecosystem, including microbial, biochemical, immunological and metabolic parameters. In WP2, short-term intervention challenges were applied to gain understanding of the dynamic interplay in the oral ecosystem following a perturbance. In WP3 a systems-biology network model was built using data derived from WPs 1 and 2. In WP4, in vitro biofilm models were used to explore the interactions between bacteria within an oral biofilm, and interactions between salivary components and the microbial biofilm. WP5 aimed to identify the interplay between saliva, oral microbial components and the host cells that line the oral cavity: the gingiva, tongue and/or buccal side. This was achieved via high-content high-throughput microscopy. The in vitro studies provided mechanistic insight into microbiota-host-saliva interactions, and could support the biomarkers identified in WPs 1-3. The importance of knowledge dissemination was emphasised by the inclusion of a separate work package (WP6) that specifically focussed on translating scientific insights for (future) healthcare professionals, the general public, legislators and policymakers.

A clinical evaluation study was completed (WP1) which assessed and identified the boundaries of a healthy oral ecosystem. This study involved 268 healthy volunteers. Via the study we established an extensive set of clinical (oral) health parameters, including gingival bleeding and caries levels. Furthermore, samples were collected for an extensive assessment of the composition of the oral ecosystem, including:

  • microbiota analysis of saliva, interproximal plaque, supragingival and subgingival plaque, and the posterior and anterior tongue biofilms
  • concentration range of 10 salivary proteins with known relevance to oral health
  • salivary peptide profiles via MALDI-TOF analysis
  • the salivary metabolome, levels and function of oral polymorphonuclear neutrophilic granulocytes (oPMNs)

Through application of advanced, statistical, machine-learning techniques we identified subgroups of healthy individuals that differed in their microbial, biochemical or metabolic oral profiles. Work is ongoing to provide better understanding of the functional significance of these differences.

In parallel, in vitro models were established for the dental microbial biofilm as well as mucosal epithelial interactions. We were able to show that exposure of the dental biofilm to a particular component – that interferes with microbial communication (quorum sensing) – eliminated lactate production of oral biofilms. Also, we have been able to establish a high-throughput in vitro wound-healing assay using automated microscopy, that allows for qualitative description of the kinetics of oral-wound repair. Using this technique we were able to confirm earlier findings that an oral pathogen inhibited wound closure. We also showed that a related, commensal species enhanced wound closure.

A clinical intervention study to explore the dynamic (biochemical, microbial and immunological) interactions of the oral ecosystem upon perturbance was performed and their involvement in maintenance of oral health.