Dental caries.

Dental caries is a biofilm-mediated, sugar-driven, multifactorial, dynamic disease that results in the phasic demineralization and remineralization of dental hard tissues. Caries can occur throughout life, both in primary and permanent dentitions, and can damage the tooth crown and, in later life, exposed root surfaces. The balance between pathological and protective factors influences the initiation and progression of caries. This interplay between factors underpins the classification of individuals and groups into caries risk categories, allowing an increasingly tailored approach to care. Dental caries is an unevenly distributed, preventable disease with considerable economic and quality-of-life burdens. The daily use of fluoride toothpaste is seen as the main reason for the overall decline of caries worldwide over recent decades. This Primer aims to provide a global overview of caries, acknowledging the historical era dominated by restoration of tooth decay by surgical means, but focuses on current, progressive and more holistic long-term, patient-centred, tooth-preserving preventive care.

Ecological approaches to oral biofilms: control without killing.

Humans have co-evolved with micro-organisms and have a symbiotic or mutualistic relationship with their resident microbiome. As at other body surfaces, the mouth has a diverse microbiota that grows on oral surfaces as structurally and functionally organised biofilms. The oral microbiota is natural and provides important benefits to the host, including immunological priming, down-regulation of excessive pro-inflammatory responses, regulation of gastrointestinal and cardiovascular systems, and colonisation by exogenous microbes. On occasions, this symbiotic relationship breaks down, and previously minor components of the microbiota outcompete beneficial bacteria, thereby increasing the risk of disease. Antimicrobial agents have been formulated into many oral care products to augment mechanical plaque control. A delicate balance is needed, however, to control the oral microbiota at levels compatible with health, without killing beneficial bacteria and losing the key benefits delivered by these resident microbes. These antimicrobial agents may achieve this by virtue of their recommended twice daily topical use, which results in pharmacokinetic profiles indicating that they are retained in the mouth for relatively long periods at sublethal levels. At these concentrations they are still able to inhibit bacterial traits implicated in disease (e.g. sugar transport/acid production; protease activity) and retard growth without eliminating beneficial species. In silico modelling studies have been performed which support the concept that either reducing the frequency of acid challenge and/or the terminal pH, or by merely slowing bacterial growth, results in maintaining a community of beneficial bacteria under conditions that might otherwise lead to disease (control without killing).

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.