An Atlas of Bacterial Physiology in the Human Oral Cavity

About This Grant

PROJECT SUMMARY/ABSTRACT Periodontitis, caries, and halitosis are highly prevalent, have a large financial burden, and negatively impact quality of life. These conditions are each driven by the community of microbes in the mouth, especially oral pathogens. In contrast, during oral health, the oral microbiota is dominated by commensal, non-pathogenic species that are thought to modulate health, including through their interactions with pathogens. Select oral microbes are well characterized in the lab, but the behavior of these organisms in the human oral cavity is not well described. Over the last decade, researchers have used RNA sequencing directly from the human oral cavity (metatranscriptomics) to define the overall bacterial behavior in subgingival plaque, in supragingival plaque, and on the tongue. These studies were instrumental in uncovering broad changes in bacterial gene expression between health and diseased states. However, there remains a lack of understanding of the behavior of individual taxa in the human oral cavity. We recently started to address this gap in knowledge by characterizing the gene expression of the pathogen Porphyromonas gingivalis during periodontitis in 93 human metatranscriptomes. This proposal expands on our approach by leveraging 697 publicly-available human oral metatranscriptomes to identify the gene expression of key oral pathogens, pathobionts, and commensals across oral sites and disease states. This study will be supported by pangenomic approaches to capture the gene expression of diverse genotypes and an in silico validation approach to ensure high specificity and sensitivity. Our findings will uncover the biology of each microbe during oral health and disease, including virulence factor expression, metabolic processes, and other host-microbe and microbe-microbe interactions. Also, we will examine the variation in behavior for each taxon of interest across hosts, oral sites, and disease states. Finally, these analyses will help researchers identify key genes to study based on the expression levels in the human oral cavity. To this end, we will share our data using interactive interfaces in the Human Oral Microbiome Database, an expertly-curated and highly-used resource for oral microbiologists. In sum, this project will be instrumental in describing the gene expression of oral microbes in the human oral cavity, uncovering new biology of these important bacteria, and empowering researchers to study genes relevant to human health and disease.