Journal of Molecular Biology
ReviewThe Structure of Dental Plaque Microbial Communities in the Transition from Health to Dental Caries and Periodontal Disease
Introduction
Numerous molecular-based sequencing studies have resulted in a consensus among researchers that approximately 700 species or phylotypes comprise the bacterial component of the oral microbiome, while each individual human is estimated to carry a subset of between 50 and 200 species [1], [2]. The human oral cavity includes different habitats for microbes including the epithelial mucosa; the papillary surface of the tongue dorsum; and the non-shedding, hard surfaces of the teeth, which themselves consist of two distinct compartments: the supragingival surface, that is, above the gum line, and the subgingival, that is, that below the gum line [2]. Site-specific, DNA sequencing studies of these different habitats have revealed that these different habitats support different microbial communities mediated by the characteristics of the surfaces available for attachment, oxygen availability, and exposure to host products delivered by saliva, to supragingival communities, and gingival crevicular fluid (GCF), to subgingival communities [3].
Dental caries are lesions of the tooth enamel and may involve the underlying dentin, which develop as a consequence of dietary sugar-driven microbial growth and carbohydrate metabolism that leads to localized acidification and disruption of tooth mineralization homeostasis [4]. Periodontitis is a chronic, progressive disease, characterized by expansion of the microbial biofilm at the gingival margin with the formation of an inflammatory infiltrate that contributes to destruction of connective tissue attachment to the tooth, alveolar bone resorption and may result in eventual tooth loss [5], [6]. In addition, periodontal disease status is correlated with certain comorbid systemic diseases including cardiovascular disease, rheumatoid arthritis, adverse pregnancy outcome, and cancer through cellular and molecular mechanisms that are not well understood [6], [7], [8], [9], [10], [11], [12].
Dental caries and periodontal disease are both mediated by the oral microbiome and host interactions and inputs: diet in the case of caries and the immune system in the case of periodontal disease [4]. The transitions from health to caries pathology and to periodontal disease are both recognized to be caused not by introduction of exogenous pathogens, but by changes in microbial community structure, that is, taxonomic composition and relative abundance, that transform the communities into pathogenic states [13]. In fact, periodontal disease is correlated with an increase in microbial community diversity, in contrast to most diseases known to be mediated by the human microbiome [5], [14], [15]. The transition from oral health to disease is further recognized to be multi-factorial, interdependent between host and microbiota and dynamic [4].
Molecular sequencing-based approaches have revolutionized our understanding of the human microbiome. Next-generation DNA sequencing and other -omics technologies have permitted the assessment of the oral microbiome with enormous breadth and without the need for prior knowledge of the system, allowing the analysis of large sample sets and facilitating large-scale, longitudinal studies that together have greatly informed our understanding of the shift in microbial community structure that occurs in the transition from health to disease [5], [16], [17], [18]. At the same time, the genetic and biochemical manipulation of individual organisms and small consortia under controlled laboratory conditions has permitted the identification of many of the molecular and cellular processes that underlie community function [19], [20], [21], [22], [23], [24]. Importantly, the network of fine scale interactions that have been identified to date does not exist in an unstructured milieu. In fact, the highly non-random structure of supragingival dental plaque has been reported in a rich body of literature, with increasing taxonomic specificity [25]. Early electron and light microscopy-based studies allowed the development of two central hypotheses to the formation of dental plaque and its role in mediating disease, namely, that highly ordered communities result as a consequence of ecological succession and that no single pathogenic organism is responsible for periodontal disease [26], [27]. This review presents a summary of the current state of knowledge regarding dental plaque structure and especially considers the importance of structure in the transition from dental health to caries pathology and periodontal disease.
Section snippets
Taxonomic Composition of Dental Plaque Communities in Health
The species composition and relative abundance of microbial communities is often referred to as community structure in the literature [3]. This type of structural information generated by sample homogenization and subsequent molecular identification through DNA sequencing is not to be confused with information on the physical architecture of microbial biofilms [28]. This type of structural information generated by direct observation with microscopy will be considered in detail subsequently.
Role of the Oral Microbiome in Health
Emerging evidence suggests that the human microbiome performs diverse functions that are beneficial for the human host [35]. The beneficial effects of the human microbiome have primarily been observed in the gut; however, recent work has identified key beneficial functions of the oral microbiota [36], [37], [38], [39]. It is hypothesized that a primary function of resident microbes is to act as a physical and biochemical barrier to prevent colonization or infection by exogenous organisms [40].
Dental Plaque Physical Structure in States of Oral Health
Early light and electron microscopy studies of intact dental plaque revealed these communities to be highly structured, with non-random distributions of morphologically and phenotypically different cells [26], [27], [53], [54]. Dental plaque is now recognized as a polymicrobial biofilm, defined as a community of microbial cells embedded in an extracellular matrix, that grows on an interface between two phases of matter, for example, the solid tooth surface and liquid saliva or GCF [55]. The
Community Structure in the Context of Dental Caries
Mutans streptococci, especially Streptococcus mutans, as well as lactobacilli are strongly correlated with caries [13]. S. mutans readily ferments sucrose and other sugars to produce ATP and lactic acid as a waste product [69]. The accumulation of lactate is thus responsible for the local acidification of the caries environment [70], [71]. Species of the aciduric, that is, acid-tolerant genus Veillonella utilize lactate as a carbon source and thus are involved in syntrophic metabolism of
Supragingival Plaque Biofilm Structure and Caries Development
Although the systems-level spatial analysis of caries-associated dental plaque biofilms with taxonomic resolution as described above for health-associated biofilms is yet to be achieved, mounting evidence assembled from different studies suggests an intrinsic contribution of spatial structure on the development of caries (Fig. 1). In the absence of abundant fermentable carbohydrates, Mitis group streptococci bind to the saliva-coated tooth with greater avidity than S. mutans, they grow more
Community Structure in the Context of Periodontal Disease
As with caries, no single organism is implicated in the transition from health to periodontal disease, rather the subgingival microbial community present in states of periodontal health transitions to a state of dysbiosis in which the community structure, that is, species composition and abundance, shifts toward a pathogenic state [83]. Early culture-independent approaches first identified a three-member consortium of Gram negative organisms, called the “Red Complex” enriched in the subgingival
Subgingival Plaque Biofilm Structure and Periodontal Disease Development
As described above, an understanding of the synergistic activities of subgingival microbes and the host as these communities undergo dysbiosis is emerging; however, what remains poorly understood is how these activities are distributed within the physical architecture of microbial communities [98]. The molecular cross-talk that takes place between the subgingival microbiota and the host immune system does not take place in an unstructured milieu, but rather within a highly ordered environment.
Early Events During the Transition from Health to Periodontal Disease
In a longitudinal metatranscriptomic study of long-term healthy subgingival sites and sites that progressed to periodontal disease in human subjects, P. gingivalis displayed upregulation of a large number of virulence genes in healthy sites that later progressed to disease, while T. denticola and T. forsythia did not upregulate any but one or a few virulence genes until later timepoints during disease progression, suggesting that when present, P. gingivalis serves as a microbial driver in the
Conclusions and Future Directions
Both dental caries and periodontal disease are highly prevalent within the human population. Both diseases are polymicrobial in their etiology and result when the supra- and subgingival microbial communities associated with states of health experience a homeostasis breakdown and undergo dysbiosis. The etiologies of these diseases are multifactorial and depend on synergistic activities, both chemical and physical, within the microbial communities and between the host diet and behavior in the
Acknowledgment
The work of the author is supported by the US National Institutes of Health (Grant DE028042).
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