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The oral microbiota: dynamic communities and host interactions

Abstract

The dynamic and polymicrobial oral microbiome is a direct precursor of diseases such as dental caries and periodontitis, two of the most prevalent microbially induced disorders worldwide. Distinct microenvironments at oral barriers harbour unique microbial communities, which are regulated through sophisticated signalling systems and by host and environmental factors. The collective function of microbial communities is a major driver of homeostasis or dysbiosis and ultimately health or disease. Despite different aetiologies, periodontitis and caries are each driven by a feedforward loop between the microbiota and host factors (inflammation and dietary sugars, respectively) that favours the emergence and persistence of dysbiosis. In this Review, we discuss current knowledge and emerging mechanisms governing oral polymicrobial synergy and dysbiosis that have both enhanced our understanding of pathogenic mechanisms and aided the design of innovative therapeutic approaches for oral diseases.

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Fig. 1: Biogeography of oral microbiota colonization in the diverse habitats of the oral cavity.
Fig. 2: Interactions among bacterial species that affect nososymbiocity.

Part a adapted with permission from ref.56, Wiley-VCH.

Fig. 3: Diet–microbiota interactions trigger the assembly of cariogenic biofilm microenvironment.

Adapted with permission from ref.7, Cell Press.

Fig. 4: Reciprocally reinforced interactions between dysbiosis and inflammation drive chronic periodontitis.
Fig. 5: P. gingivalis induces dysbiosis by impairing innate host defences while promoting inflammatory responses in phagocytic cells.
Fig. 6: Localized chemokine paralysis.

Adapted with permission from ref.10, Cell Press.

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Acknowledgements

The work of the authors is supported by US National Institutes of Health grants DE01111, DE012505, DE017921 and DE0130585 (R.J.L.); DE018023, DE025220 and DE025848 (H.K.); and DE015254, DE024153, DE024716, DE026152 and AI068730 (G.H.).

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Nature Reviews Microbiology thanks G. Belibasakis, B. Keijser and other anonymous reviewers for their contributions to the peer review of this work.

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R.J.L., H.K. and G.H. researched the data for the article, substantially contributed to discussion of content, wrote the article and reviewed and edited the manuscript before submission.

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Correspondence to Richard J. Lamont or Hyun Koo or George Hajishengallis.

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Glossary

Subgingival

Relating to the area under the gum margins.

Gingival crevicular fluid

(GCF). A serum exudate that contains immune and inflammatory mediators, along with large numbers of neutrophils recruited along a chemokine gradient.

Extracellular polymeric substances

(EPS). Extracellular biomolecules including exopolysaccharides, fibrous and globular proteins in addition to extracellular enzymes, lipids and nucleic acids.

Gingivitis

Mild and reversible inflammation of the gum often accompanied by bleeding upon toothbrushing. Tissue destruction does not occur. Gingivitis results from an accumulation of the plaque biofilm around the gingival margin and resolves after removal of the plaque.

Acidogenic

Organisms capable of producing acidic metabolites and reducing environmental pH.

Dysbiosis

An imbalanced interaction that can be among bacteria in a community or between the microbiome and the host, and is detrimental to the host. The imbalance can be in the amount and/or the influence of individual microbial species relative to their abundance or influence in health. Alternatively, the imbalance can be caused by a poorly controlled immune response.

Periodontitis

An episodic, slowly progressing inflammatory disease of the periodontal tissues that usually occurs in adults, although aggressive, rapidly progressing forms exist and can occur in adolescents.

Dental caries

A polymicrobial and diet-dependent disease that is characterized by the development of pathogenic biofilms (dental plaque) within which acid production from bacterial metabolism of dietary carbohydrates causes demineralization of the mineralized tooth tissues (enamel, dentin and cementum), eventually leading to the clinical onset of cavitation or tooth decay.

Aciduric

Organisms capable of growth at acidic pH levels that are often toxic to other bacteria.

Polymicrobial synergy

Interactions among organisms that increase microbial fitness in the local environment.

Dentin

Calcified tissue, predominantly hydroxyapatite, forming the bulk of the tooth, which is beneath and is softer (less mineralized with more organic material) than enamel.

Periodontal diseases

A collection of conditions in which poorly controlled inflammatory responses induced by the microbiota cause destruction of the supporting structures of the tooth.

Red complex

The triad of P. gingivalis, T. forsythia and T. denticola — organisms that are often isolated together and were classically considered to be the predominant pathogens in chronic periodontitis.

Gingival crevice

The compartment between the tooth root and the gingival (gum) tissue. The gingival crevice deepens into a periodontal pocket as periodontal disease progresses and tissue is destroyed.

Citrullinate

Post-translational modification of a protein involving deamination of arginine by the enzyme peptidylarginine deiminase PPAD to produce citrulline.

Cross feeding

The utilization of a metabolic by-product of one organism as a nutrient source by another organism.

Nososymbiocity

The potential for a microbial community to contribute to disease; this recognizes the community rather than a single species as the aetiological agent.

Salivary pellicle

A layer of salivary proteins and glycoproteins adsorbed to the enamel surface and to which adhesins of initial colonizers of the oral surface can attach. Pellicle can also contain molecules of microbial origin and those derived from epithelial cells.

Accessory pathogen

Organisms that act synergistically with more pathogenic species (keystone pathogens or pathobionts) to elevate community nososymbiocity. Accessory pathogens can provide an attachment substratum for colonization and metabolic support, and can increase virulence gene expression in other organisms through physical interactions or small-molecule-dependent communication.

Keystone pathogen

Species that exert an influence on their communities that is disproportionate relative to their abundance and therefore form the ‘keystone’ of the community’s structure.

Homeostatic commensals

Species that act to maintain a host–microbiota equilibrium by mitigating the action of more pathogenic species. Mechanisms include reducing the impact of pathogens on host cell signalling pathways or production of metabolites that favour a homeostatic inflammatory response.

Homeostasis

A state of equilibrium or stability in a system that is maintained by adjusting physiological processes to counteract external changes.

Ecological plaque (biofilm) hypothesis

A model encompassing microbiological, biochemical and ecological properties of oral biofilms and their association with disease. The model also accommodates host-derived changes (for example, frequent dietary sugar exposure) that trigger changes in the nososymbiocity of biofilm communities.

Saccharolytic potential

The ability of an organism to metabolize carbohydrates.

Emergent properties

Novel structures, activities, patterns and properties that arise during self-organization into complex systems. In the context of biofilm communities, these include surface adhesion and interbacterial cohesion, spatial organization, physical and social interactions, chemical heterogeneity and increased tolerance to antimicrobials.

Pathobionts

Organisms that are generally benign or commensal within an indigenous community but transition to pathogenic upon the breakdown of host–microbiota homeostasis (for example, as a result of antibiotic treatment, tissue damage, dietary shifts and especially immune deficiencies). These conditions promote pathobiont outgrowth and disrupt the symbiotic microbiota, causing further dysbiosis and inflammation.

Asaccharolytic

A property of organisms incapable of breaking down carbohydrates for energy and thus reliant on the degradation of proteins and the generation of amino acids for metabolic energy and growth.

Inflammophilic

A property of bacteria that thrive on inflammation and utilize inflammatory tissue breakdown products for nutrition.

Hemin

An iron-containing porphyrin compound released from red blood cells; exploited by bacteria to obtain iron for growth.

Localized chemokine paralysis

Precise and targeted suppression of specific chemokines by microbial community participants, superseding the otherwise stimulatory activity of other community inhabitants.

Black queen hypothesis

A theory of reductive evolution to account for co-dependency.

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Lamont, R.J., Koo, H. & Hajishengallis, G. The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol 16, 745–759 (2018). https://doi.org/10.1038/s41579-018-0089-x

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