The oral microbiome and the immunobiology of periodontal disease and caries

Abstract

The composition of the oral microbiome differs from one intraoral site to another, reflecting in part the host response and immune capacity at each site. By focusing on two major oral infections, periodontal disease and caries, new principles of disease emerge. Periodontal disease affects the soft tissues and bone that support the teeth. Caries is a unique infection of the dental hard tissues. The initiation of both diseases is marked by an increase in the complexity of the microbiome. In periodontitis, pathobionts and keystone pathogens such as Porphyromonas gingivalis appear in greater proportion than in health. As a keystone pathogen, P. gingivalis impairs host immune responses and appears necessary but not sufficient to cause periodontitis. Historically, dental caries had been causally linked to Streptococcus mutans. Contemporary microbiome studies now indicate that singular pathogens are not obvious in either caries or periodontitis. Both diseases appear to result from a perturbation among relatively minor constituents in local microbial communities resulting in dysbiosis. Emergent consortia of the minor members of the respective microbiomes act synergistically to stress the ability of the host to respond and protect. In periodontal disease, host protection first occurs at the level of innate gingival epithelial immunity. Secretory IgA antibody and other salivary antimicrobial systems also act against periodontopathic and cariogenic consortia. When the gingival immune response is impaired, periodontal tissue pathology results when matrix metalloproteinases are released from neutrophils and T cells mediate alveolar bone loss. In caries, several species are acidogenic and aciduric and appear to work synergistically to promote demineralization of the enamel and dentin. Whereas technically possible, particularly for caries, vaccines are unlikely to be commercialized in the near future because of the low morbidity of caries and periodontitis.

Keywords: Caries; Microbiome; Pathogenesis; Periodontitis.

Figure 1

Anatomy and ecological niches of the oral cavity.

Figure 2. Microbial diversity and richness in periodontal health and disease

Microbial communities with lower diversity and richness harbor keystone pathogens, symbionts and pathobionts at very low frequency and in proportions adequate to ensure health. When environmental perturbations occur in the periodontal tissues (e.g., trauma or idiopathic growth of a keystone pathogen) or the host is genetically susceptible, keystone pathogens elicit inflammation that changes the nutrient foundation of the ecological niche (i.e. periodontal pocket). The altered nutrient foundation promotes the proportional expansion of pathobionts relative to symbionts, promoting inflammation that ultimately leads to connective tissue and bone destruction. Diversity and richness are higher.

Figure 3

Proportions of oral microorganisms in the Human Oral Microbiome Database (HOMD) [5].

Figure 4. CORE microbiome of oral cavity

The tree was generated with RAxML BlackBox Web server [154] and viewed in ITOL [155]. Genera are color-coded by phyla, except for the Firmicutes and Proteobacteria, which are shown at the level of class (Adapted from [6]).

Figure 5. Proportions of different genera recovered from whole saliva of healthy adults

Saliva was collected from a group of 71 healthy individuals by mouthrinse with 10 mL UV-irradiated sterile saline for 30 sec and stored at −80°C. The asterisks (*) denote the best classification possible as adapted from a table in [20].

Figure 6. Selective coaggregation and relative abundance of microorganisms in supra/subgingival dental plaque of humans

(A) Spatial analysis of human dental plaque using Combinatorial Labeling and Spectral Imaging - Fluorescence In Situ Hybridization (CLASI-FISH) strategy reveals specific interactions between certain microorganisms and not with others. (B) The 2D plot reveals the relative abundance (diameter of circles) and intertaxon associations observed between labeled taxons. A line connecting two taxa indicates that cells of the lower-abundance taxon of any pair were observed to associate with cells of the higher-abundance taxon with >3% frequency and more frequently than would be expected from random associations. (Adapted with permission from Valm A.M. et al. PNAS 2011;108:4152–4157.)

Figure 7. Proportions of different genera recovered from dental plaque of healthy adults

Supragingival plaque from a group of 98 healthy individuals by sampling cheek-side dental surfaces using a sterile, DNA-free wooden toothpick and stored at −80°C. The asterisks (*) denote the best classification possible as adapted from a table in [20].

Figure 8. Diversity and richness of microbial communities directly relate to caries risk

Microbial communities of the tooth surface and irregularities in the enamel differ with respect to diversity and richness. Surfaces and sites with highest diversity and richness mature at ecological niches most susceptible to caries. When caries is established, the acid environment reduces the diversity and richness of the local microbiota.

Figure 9. Microbiome of the periodontal pocket in health and disease

Subgingival samples were collected form pockets < 4 mm (healthy) or > 5mm (diseased) in depth. After the removal of supragingival plaque and drying the target sites, samples were collected by insertion of four medium paper points for 10 s into three sites. Deep and shallow sites were sampled separately in subjects with periodontitis. (Adapted with permission from Griffen AL. et al. ISME J. 2012 Jun;6(6):1176–85)

Figure 10. Frequency distribution of periodontal microorganisms in periodontitis patients with ≥ 4mm pockets and in healthy individuals

Data show differences between health and disease at level of phylum, genus and species. Pie charts indicate the number of taxa that were significantly different. The graphs show levels for genera that were ≥ 0.1% different and species that were ≥ 0.2% different in health and periodontitis samples. Taxa were sorted according to magnitude of change. P ≤ 0.05 after FDR correction for all taxa shown. (Adapted with permission from Griffen AL. et al. ISME J. 2012 Jun;6(6):1176–85)