Exploiting the Oral Microbiome to Prevent Tooth Decay: Has Evolution Already Provided the Best Tools?
Baker JL, Edlund A
Front Microbiol. 2018. doi: 10.3389/fmicb.2018.03323
COMMENT: This minireview describes therapeutic strategies for caries prevention and treatment that exploit the protective effects of the healthy oral flora to prevent dental caries.
Commensal oral microbiota displays colonization resistance. It maintains a stable oral microbiome and protects from pathogens colonization. The increase in carbohydrate consumption appears to be responsible for the high prevalence of dental caries (affecting 60–90% of children and adults in industrialized countries). It has fostered the development of novel modalities to prevent caries. The most promising strategies target the healthy oral microbiome:
This review highlights therapeutic strategies, both contemporary and developing, that exploit the protective effects of the healthy oral flora in an effort to prevent dental caries
About the healthy flora:
Typically, the earliest colonizers of the tooth surface are commensal streptococci, such as Streptococcus mitis, Streptococcus sanguinis, Streptococcus gordonii, and other closely related taxa. These species are the most avid binders of the naked, pellicle-coated tooth surface. Once these species have bound, they provide a more complex substrate to which other species can now bind. To help ensure their continued success, the majority of taxa within the mitis and sanguinis groups stanchly antagonize newcomers using the production of alkali, bacteriocins, and H2O2. In the absence of a carbohydrate-rich diet, these commensal streptococci tend to remain at high abundances in dental plaque. This dominance is strongly associated with good dental health
About the cariogenic flora:
With frequent consumption of carbohydrates, particularly when concurrent with a lack of oral hygiene, increased bacterial production of a glucan matrix is favored, emeshing cells and preventing diffusion of metabolites. This allows for development of emergent properties of the dental plaque, such as acidic microenvironments resulting from carbohydrate fermentation. Typically, the saliva in the mouth has sufficient buffering capacity to neutralize the organic acids produced by bacterial metabolism, and repair acid-damaged enamel. However, the increased thickness and density of exopolysaccharide-rich plaque prevents both diffusion of saliva into the biofilm and diffusion of acids out of the biofilm. The commensal early colonizers are comparatively not well-adapted to acidic conditions, allowing for a further enrichment of acid-tolerant (aciduric) taxa such as Streptococcus mutans, Veillonella spp., and Lactobacillus spp. With progression of this positive feedback loop, the rate of net acid damage (demineralization) of the tooth enamel outpaces repair (remineralization), leading to clinical disease.
S. mutans is particularly adept at producing a glucan matrix from sucrose, and therefore is considered a keystone species in caries pathogenesis
These are the most important strategies for prevention and treatment of caries described in this minireview:
- A low sucrose diet to avoid the formation of cariogenic biofilms
- Fluoride to improve remineralization of tooth enamel and to inhibit the metabolism of cariogenic bacteria
- Prebiotics: arginine, Met-Pro, succinic acid, beta-methyl-d-galactoside and N-acetyl-d-mannosamine (rigourose clinical trials are needed)
- Polyol gums that increase saliva removing bacteria from the tooth surface
- Probiotics to prevent the outgrowth of pathogenic species as Streptococcus mutans
- Vaccination to increase secretory IgA levels against S. mutans and other cariogenic targets
- Antimicrobial peptides against cariogenic bacteria
- Small molecules to provoke the disruption of S. mutans biofilms
- Bacteriophages lytic for cariogenic pathogens
The development of novel caries therapeutics has focused on S. mutans. However, it is not the singular cause of the disease. The best option to fight against caries could be based on our healthy flora and their natural products:
Fortunately, evolution has shaped territorial commensal taxa which antagonize cariogenic species. Exploitation of this relationship, whether by directly supporting the dominance of commensal taxa, or via targeted killing of their pathogenic competitors, is a promising course of therapeutic development. Although several of these approaches have produced encouraging results, properly controlled rigorous human studies are needed, the cost of which is likely to be a significant deterrent. Nevertheless, there is room for optimism, as it appears evolution may have already provided the best tools in the form of our commensal defenders and their natural products.