Transmission tracking dental disease
By the time we reach the age of 75, ~26% of us will have had all teeth extracted. Full mouth extraction tends to be necessary in mid-life in those with generalized caries or periodontal disease or in individuals needing prosthetics. Due in part to oral hygiene and the activity of salivary flow, dental cavities are usually restricted to the biting surfaces of teeth in the back of the mouth. Anterior teeth (incisors, canines) become vulnerable to cavities in response to perturbations – for example, in response to the chronic use of methamphetamines or even simply the concomitant use of multiple medications, high frequency/high sugar diets, the loss of salivary gland function, or aging. An important question is whether anterior sites, in these contexts, become vulnerable to cavities due to an increase in microbial dispersal, defined here as the movement of microbes from one tooth to another. My group will answer this question using the methods of genomic epidemiology.
Comparative genomics of the oral microbiome
A second major focus in my group will be to strategically sample animals across the tree of life, performing comparative analysis of spatial patterning of teeth and oral microbiomes. In the long term, we aim to isolate the influence of tooth composition (e.g., dentine, enameloid, enamel) and host physiology or anatomy (salt or salivary glands & tooth crowding) on the spatial architecture of the oral microbiome. Results are expected to identify aspects of host anatomy and physiology that govern the oral microbiota which in turn mediates health and disease.
Spatial ecology of the human oral microbiome
Trained in statistics by Susan Holmes, I applied multivariate spatial methods (trend surface analysis, moran’s eigenvector maps, etc.) to microbiome data collected at high spatial resolution. I identified a spatial gradient in the communities that inhabit the oral cavity, whether on teeth, the buccal mucosa, alveolar mucosa, or keratinized gingiva. These methods can be used broadly to investigate the spatial ecology of communities at any body site or indeed at any system where geographic coordinates (x, y) are obtained. This work is significant because we demonstrate that periodic disturbances, which are induced by salivary flow are needed to maintain the gradient of bacterial diversity.
Examining the spatial distribution of dental disease
In collaboration with Christof Seiler I constructed a series of tooth-specific linear models to quantify the extent to which patient cohort, age, and Unstimulated Whole Salivary Flow Rate (UWS-FR) are associated with the increment of dental and periodontal disease at each tooth. Our findings suggest that while age and a presumptive diagnosis of Sjogren’s Syndrome correlate with the site-specific increment of disease so too does unstimulated whole salivary flow rate (UWS-FR). Not only is decreasing UWS-FR associated with increasing decayed, missing, filled surfaces (DMFS) at 21 teeth, but it is also associated with increased recession, as measured by clinical attachment loss (CAL), at 10 teeth. These data suggest that salivary flow influences the site specific increment of caries and periodontal disease at a wider number of teeth than previously appreciated. In addition, we performed a pilot experiment and demonstrate that microbial dispersal is elevated at sites above the gumline in patients with low salivary flow. This work is important because it links spatial patterns of disease to spatial patterns in the distribution of microbes.
Body site occupancy and the emerging fungal pathogen Candida auris
In collaboration with the Centers for Disease Control (CDC) and infectious diseases physicians at the NIH and Rush University, I used culture data, ITS1 sequencing, and whole genome sequencing to characterize the distribution of Candida auris between and across skin sites on the human body. My data revealed that surveillance of at least 6 body sites is required to identify all colonized patients, which implies occult colonization of sites not under routine surveillance may underlie ongoing transmission in facilities experiencing recalcitrant outbreaks. We are currently innovatively integrating whole genome sequencing with metagenomics to understand patterns of transmission, of Candida auris, between and across body sites.