Exploiting the Oral Microbiome to Prevent Tooth Decay: Has Evolution Already Provided the Best Tools?

Abstract

To compete in the relatively exposed oral cavity, resident microbes must avoid being replaced by newcomers. This selective constraint, coupled with pressure on the host to cultivate a beneficial microbiome, has rendered a commensal oral microbiota that displays colonization resistance, protecting the human host from invasive species, including pathogens. Rapid increases in carbohydrate consumption have disrupted the evolved homeostasis between the oral microbiota and dental health, reflected by the high prevalence of dental caries. Development of novel modalities to prevent caries has been the subject of a breadth of research. This mini review provides highlights of these endeavors and discusses the rationale and pitfalls behind the major avenues of approach. Despite efficacy, fluoride and other broad-spectrum interventions are unlikely to further reduce the incidence of dental caries. The most promising methodologies in development are those that exploit the exclusive nature of the healthy oral microbiome. Probiotics derived from the dental plaque of healthy individuals sharply antagonize cariogenic species, such as Streptococcus mutans. Meanwhile, targeted antimicrobials allow for the killing of specific pathogens, allowing reestablishment of a healthy microbiome, presumably with its protective effects. The oral microbiota manufactures a massive array of small molecules, some of which are correlated with health and are likely to antagonize pathogens. The prohibitive cost associated with sufficiently rigorous clinical trials, and the status of dental caries as a non-life-threatening condition will likely continue to impede the advancement of new therapeutics to market. Nevertheless, there is room for optimism, as it appears evolution may have already provided the best tools.

Keywords: Streptococcus; antimicrobial small molecules; caries; oral probiotics; oral treatment.

FIGURE 1

(A) Overview of caries pathogenesis. Early colonizers of the tooth are mainly health-associated streptococcal species, such as S. sanguinis and S. gordonii, as well as other closely related taxa. Poor oral hygiene, a high-sugar diet, and other salivary, immunological, and microbial factors lead to development of pathogenic biofilms (i.e., dysbiosis). S. mutans produces a glucan matrix, which leads to robust biofilm formation and colonization by taxa which could not have bound the tooth surface unassisted (late colonizers). Production of acid within the biofilm selects for increasingly acid-tolerant cariogenic organisms, such as S. mutans, Lactobacillus spp., Veillonella spp., and others. Unchecked, the process will destroy the protective enamel coating of the tooth and lead to clinical disease. (B) Preventative and therapeutic modalities in current use or development. A diet low in refined sugars, such as sucrose, will inhibit production of glucans and formation of cariogenic biofilms. Fluoride both promotes remineralization of tooth enamel and inhibits potentially cariogenic bacterial metabolism. Polyol gums increase saliva flow, delivering ions for tooth remineralization and promoting clearance of bacteria from the tooth surface. Probiotics antagonize and prevent establishment and outgrowth of pathogenic species, such as S. mutans. Immune priming via vaccination leads to elevated levels of secretory IgA, which binds target epitopes on S. mutans and other cariogenic targets, preventing binding and biofilm formation, and promoting clearance from the oral cavity. Antimicrobial peptides, STAMPS, small molecules, and phage promote targeted killing of specific cariogenic taxa, such as S. mutans.