School of Dentistry
Although the etiology of dental caries is multifactorial, frequent consumption of fermentable carbohydrates, notably sucrose, appears to be a major factor driving the supragingival microbiota in the direction of dysbiosis. Recent 16S rDNA-based studies indicate that caries-associated communities were less diverse than healthy supragingival plaque overall, but still displayed considerable taxonomic diversity between individuals. A key finding of the Human Microbiome Project was that healthy sites from different people were broadly similar with respect to gene function, even though there was extensive individual variation in their taxonomic profiles. That pattern may also extend to dysbiotic communities. In that case, shifts in community-wide protein expression might provide more sensitive and specific biomarkers of dysbiosis than can be achieved through taxonomy alone. The preliminary 2D MSMS metaproteomic data for this project suggest that sucrose–induced changes in protein expression patterns are conserved in taxonomically diverse oral microcosm biofilm communities. Those data provide the foundation for the goals of this research, which are to use shotgun metaproteomics of oral microcosm biofilm communities to to validate preliminary findings, determine whether sucrose also induces dysbiosis in microcosms from caries-free children, and discover protein function biomarkers of sucrose-induced dysbiosis that could later be used to develop assays for early detection of dysbiosis in dental plaque.
The project includes the following specific aims:
- Conduct metagenomic/metaproteomic analyses of biofilm microcosms grown from plaque collected from 50 caries-active children, to validate preliminary observations that changes in protein expression are more consistent indicators of sucrose-induced dysbiosis than are shifts in the taxonomic diversity of potentially cariogenic species
- Conduct metagenomic/metaproteomic studies of biofilm microcosms grown from plaque collected from 50 caries-free children, to test the hypothesis that they may be more resistant to sucrose-induced dysbiosis than microcosms from caries-active children
- Use bioinformatic and biostatistical analysis of both datasets to discover whether there are a subset of biomarkers that distinguish dysbiotic biofilms at levels of sensitivity and specificity sufficient to justify future development of assays for early detection of dysbiosis