A Quantitative Framework for Characterizing Oral pH Dynamics

Abstract

Dental caries is a polymicrobial biofilm-based disease whereby acidogenic and aciduric microorganisms within dental plaque generate an acidic milieu resulting in dissolution of enamel and dentin below their critical pH. The relationship of pH over time following exposure to a cariogenic substrate, coined the “Stephan curve,” continues to be a critical determinant in whether a substance is deemed cariogenic. Several caries-associated parameters can be extracted from the data, including minimum pH, time corresponding to the minimum pH, recovery time, time below the critical pH, and area below the critical pH. While wire telemetry devices were developed for continuous recording of plaque pH in vivo, most clinical datasets use the indirect method or strip method due to patient compliance issues, ease of use, and cost limitations. Most of the time, this results in sparse sampling time points. In this work, we demonstrate how sparse datasets lead to underestimation of critical parameters associated with caries risk and can therefore alter the interpretation of the data and conclusions drawn, potentially leading to inaccurate claims. To mitigate this issue, we developed a quantitative framework that harnesses nonlinear mixed effects and fixed effects modeling to better predict these caries-associated pH parameters and show superiority as compared with traditional methods used in prior literature. We conclude by introducing a web-based and publicly available interface (GatorpH) that utilizes our mathematical models. This interface can be readily applied to plaque and saliva pH profiles that are routinely collected in clinical studies 1) assessing the potential relative cariogenicity of dietary items, 2) establishing the efficacy of novel cariostatic agents or biomaterials, or 3) characterizing changes in acidogenicity among patient populations or microbiome studies. Translational researchers, clinicians, and regulatory agencies can therefore utilize GatorpH for the study of oral pH dynamics and for rapid and reliable quantification of critical parameters associated with dental caries.