Project leader: Dr Bart Keijser
Time frame 2012 – 2016
Project code: OH001
Project login (project members only)
This project aims to identify the biological processes in the oral ecosystem responsible for maintaining oral health. The project is 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 comprises five interconnected work packages: a sixth work package is focussed on knowledge dissemination.WP1 aims to provide a detailed description of the oral ecosystem, including microbial, biochemical, immunological and metabolic parameters. In WP2, short-term intervention challenges will be applied to gain understanding of the dynamic interplay in the oral ecosystem following a perturbance. In WP3 a systems-biology network model will be built using data derived from Work Packages 1 and 2. In WP4, in vitro biofilm models will be used to explore the interactions between bacteria within an oral biofilm and interactions between salivary components and the microbial biofilm. WP5 aims 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 will be achieved via high-content high-throughput microscopy. The in vitro studies will provide mechanistic insight into microbiota-host-saliva interactions and could support the biomarkers identified in WPs 1-3. The importance of knowledge dissemination is emphasised by the inclusion of a separate work package (WP6) that specifically focuses on translating scientific insights for (future) healthcare professionals, the general public, legislators and policy makers.
During the previous two years, 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 have been 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. The findings have been patented. 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.
We are currently performing a clinical intervention study to explore the dynamic (biochemical, microbial and immunological) interactions of the oral ecosystem upon perturbance and their involvement in maintenance of oral health.
|Scientific papers in peer-reviewed journals||2015 Personalized microbial network inference via co-regularized spectral clustering||View summary|
|Scientific papers in peer-reviewed journals||2015 In vitro phenotypic differentiation towards commensal and pathogenic oral biofilms||View summary|
||2014 The oral microbiome|
|Invited lectures||2014 Saliva and the oral mircobiome|