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The oral microbiome: diversity, biogeography and human health

Nature Reviews Microbiology volume 22, pages 89–104 (2024)Cite this article

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Abstract

The human oral microbiota is highly diverse and has a complex ecology, comprising bacteria, microeukaryotes, archaea and viruses. These communities have elaborate and highly structured biogeography that shapes metabolic exchange on a local scale and results from the diverse microenvironments present in the oral cavity. The oral microbiota also interfaces with the immune system of the human host and has an important role in not only the health of the oral cavity but also systemic health. In this Review, we highlight recent advances including novel insights into the biogeography of several oral niches at the species level, as well as the ecological role of candidate phyla radiation bacteria and non-bacterial members of the oral microbiome. In addition, we summarize the relationship between the oral microbiota and the pathology of oral diseases and systemic diseases. Together, these advances move the field towards a more holistic understanding of the oral microbiota and its role in health, which in turn opens the door to the study of novel preventive and therapeutic strategies.

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Fig. 1: Biogeography of the oral microbiome and relative sizes of its members.
Fig. 2: Experimental gingivitis in humans reveals three distinct response types.
Fig. 3: Links between the oral microbiota and systemic diseases.

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Acknowledgements

The authors were supported by NIH NIDCR K99-DE029228 (J.L.B.); NIH NIDCR R01DE022586 (J.L.M.W.); NIH NIDCR R03DE030987 and R01DE016937 (K.M.K.); NIH NIDCR R01DE031470 (J.S.M.); NIH NIDCR R01DE023810 (J.S.M. and X.H.) and NIH NIDCR R01DE029479 and R01DE030943 (X.H.). The authors acknowledge the many authors whose work in this domain was not included owing to text and citation constraints and thank F. Scannapieco, F. Dewhirst, C. Matrishin, E. Haase, W. Mei, H. Koo, B. Bor, G. Lewin, M. Freire, M. Kintzing and J. Tian for feedback and ideas for Fig. 1 and the illustration in Box 2.

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Authors and Affiliations

  1. Oregon Health & Science University, Portland, OR, USA

    Jonathon L. Baker

  2. J. Craig Venter Institute, La Jolla, CA, USA

    Jonathon L. Baker

  3. UC San Diego School of Medicine, La Jolla, CA, USA

    Jonathon L. Baker

  4. The Forsyth Institute, Cambridge, MA, USA

    Jessica L. Mark Welch & Xuesong He

  5. Marine Biological Laboratory, Woods Hole, MA, USA

    Jessica L. Mark Welch

  6. University at Buffalo, Buffalo, NY, USA

    Kathryn M. Kauffman

  7. University of Washington, Seattle, WA, USA

    Jeffrey S. McLean

  8. Harvard School of Dental Medicine, Boston, MA, USA

    Xuesong He

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The authors contributed equally to all aspects of the article.

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Related links

Cenote Human Virome Database: https://zenodo.org/record/4498884

Human Oral Microbiome Database: https://homd.org/

Human Oral Virome Database: https://github.com/RChGO/OVD

IMG/VR Viral Resources: https://img.jgi.doe.gov/cgi-bin/vr/main.cgi

Supplementary information

Glossary

16S rRNA gene amplicon sequencing

A microbiome sequencing technique whereby the variable region or regions of 16S rRNA genes are amplified by PCR using primers specific to the flanking conserved regions; the amplicons are then sequenced, providing information about the presence of and qualitative information about the relative abundances of the various taxa within the sample.

Candidate phyla radiation bacteria

(CPR bacteria). A large, monophyletic group of bacteria that have reduced genomes and ultrasmall cell size and are thought to have an epiparasitic lifestyle dependent on bacterial host organism or organisms.

Combinatorial labelling and spectral imaging fluorescence in situ hybridization

(CLASI-FISH). A microscopy technique whereby each taxon of interest is labelled with multiple fluorophores to greatly expand the number of distinguishable targets. Microscopes capable of spectral imaging allow the use of fluorophores with overlapping emission spectra.

Dysbiosis

A disruption (that is, a change in taxonomic abundance, metabolism and or ecology) in the normal, health-associated microbiota that results in an ecological imbalance, frequently contributing to or resulting in a pathological state.

Fluorescence in situ hybridization-based microscopy

(FISH-based microscopy). Microscopy that uses fluorescently labelled DNA oligonucleotides complementary to specific DNA or RNA sequences as probes in FISH. Hybridization of probe to target enables cells or structures containing the sequence of interest to be observed directly using a fluorescence microscope.

Gingipains

A family of proteases secreted by the pathogen, Porphyromonas gingivalis, which can degrade cytokines and alter the host inflammatory response.

Gingival crevicular fluid

(GCF). A serum-like fluid that flows into the gingival sulcus (the gap between gums and teeth) from the blood vessels within the gingival connective tissue.

Metagenomic sequencing

A microbiome sequencing technique whereby an arbitrary subset of the DNA extracted from the sample is sequenced (as opposed to the sequencing of a targeted region by PCR, as in 16S rRNA gene amplicon sequencing), providing genomic information and taxonomic resolution that is not possible with amplicon sequencing.

Pathobiont

Opportunistic microorganism that emerges as a result of perturbations in the healthy microbiome.

Prebiotic

Compounds that foster growth or activity of microorganisms that are generally beneficial to the human host.

Probiotics

Live microorganisms that are intended to have health benefits when administered or consumed.

Syntrophy

A phenomenon (also known as cross-feeding) whereby one species is living off the metabolic products of another species.

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Baker, J.L., Mark Welch, J.L., Kauffman, K.M. et al. The oral microbiome: diversity, biogeography and human health. Nat Rev Microbiol 22, 89–104 (2024). https://doi.org/10.1038/s41579-023-00963-6

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