Non-lethal control of the cariogenic potential of an agent-based model for dental plaque

Dental caries or tooth decay is a prevalent global disease whose causative agent is the oral biofilm known as plaque. According to the ecological plaque hypothesis, this biofilm becomes pathogenic when external challenges drive it towards a state with a high proportion of acid-producing bacteria. Determining which factors control biofilm composition is therefore desirable when developing novel clinical treatments to combat caries, but is also challenging due to the system complexity and the existence of multiple bacterial species performing similar functions. Here we employ agent-based mathematical modelling to simulate a biofilm consisting of two competing, distinct types of bacterial populations, each parameterised by their nutrient uptake and aciduricity, periodically subjected to an acid challenge resulting from the metabolism of dietary carbohydrates. It was found that one population was progressively eliminated from the system to give either a benign or a pathogenic biofilm, with a tipping point between these two fates depending on a multiplicity of factors relating to microbial physiology and biofilm geometry. Parameter sensitivity was quantified by individually varying the model parameters against putative experimental measures, suggesting non-lethal interventions that can favourably modulate biofilm composition. We discuss how the same parameter sensitivity data can be used to guide the design of validation experiments, and argue for the benefits of in silico modelling in providing an additional predictive capability upstream from in vitro experiments

Dentifrices, mouthwashes, and remineralization/caries arrestment strategies

While our knowledge of the dental caries process and its prevention has greatly advanced over the past fifty years, it is fair to state that the management of this disease at the level of the individual patient remains largely empirical. Recommendations for fluoride use by patients at different levels of caries risk are mainly based on the adage that more is better. There is a general understanding that the fluoride compound, concentration, frequency of use, duration of exposure, and method of delivery can influence fluoride efficacy. Two important factors are (1) the initial interaction of relatively high concentrations of fluoride with the tooth surface and plaque during application and (2) the retention of fluoride in oral fluids after application

Urea concentration in minor mucous gland secretions and the effect of salivary film velocity on urea metabolism by Streptococcus vestibularis in an artificial plaque

Our purpose was to determine the urea concentration in minor mucous gland (MMG) secretions and the pH at proximal and distal aspects of the lower surface of artificial plaque in vitro during infusion of urea solutions over the surface, at different film velocities. Saliva is present in the mouth as a slowly moving film (ca. 0.1 mm thick) with an estimated velocity in the range of 0.8–8.0 mm/min. At low velocities, due to the accumulation of bacterial products, a progressive increase in their concentration may occur in both the plaque and the overlying salivary film at the distal edge (where the film leaves the plaque). S. vestibularis, an oral micro‐organism possessing ureolytic activity, was combined with 1% agarose, to give a urease Vmax similar to that of natural plaque. The artificial plaque was in the chamber (6.0 × 6.0 square and 0.5 or 1.5 mm deep) of a diffusion apparatus, and a urea‐containing artificial saliva (3.3 or 13.2 mmol/ 1) was infused over the surface, as a film 0.1 mm deep, at velocities of 0.8, 8.2 and 86.2 mm/min. At the lower (physiologically normal) urea concentration and the two lower film velocities, most urea appeared to be metabolized at the proximal end of the plaque, which developed a higher pH. At the higher urea concentration, and a film velocity of 8 mm/min, a higher pH was found at the distal end. This was probably due to the combination of greater urea availability and a reduced rate of ammonia loss distally. At a film velocity of 86.2 mm/min, proximal/distal pH gradients did not develop. Thus the salivary film velocity may influence the pH and ammonia level in plaque and perhaps the development of gingivitis. In unstimulated and stimulated MMG secretions, which are the secretions in contact with the buccal surfaces of most teeth, the urea concentrations were 5.27 ± 1.07 and 4.38 ± 1.51 mmol/1, respectively