Oligotyping analysis of the human oral microbiome
Open accessAbstract
Significance: The human body, including the mouth, is home to a diverse assemblage of microbial organisms. Although high-throughput sequencing of 16S rRNA genes provides enormous amounts of census data, accurate identification of taxa in these large datasets remains problematic because widely used computational approaches do not resolve closely related but distinct organisms. We used a computational approach that relies on information theory to reanalyze the human oral microbiome. This analysis revealed organisms differing by as little as a single rRNA nucleotide, with dramatically different distributions across habitats or individuals. Our information theory-based approach in combination with habitat analysis demonstrates the potential to deconstruct entire microbiomes, detect previously unrecognized diversity, and provide deep insight into microbial communities in health and disease.
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Strong site preference is additionally observed among several Actinomyces species, as well as in Corynebacterium, Fusobacterium, and Prevotella species.
“Strong site preference is additionally observed among several Actinomyces species, as well as in Corynebacterium, Fusobacterium, and Prevotella species.”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [234]
Among Streptococcus species in the oral cavity, S salivarius and Streptococcus parasanguinis are specialized for colonization on tongue dorsal surfaces, whereas S sanguinis and S gordonii instead reside in dental plaque communities.
“For example, among Streptococcus species in the oral cavity, S salivarius and Streptococcus parasanguinis are specialized for colonization on tongue dorsal surfaces, whereas S sanguinis and S gordonii instead reside in dental plaque communities.234”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [234]
Many microbial subtypes are specialized to reside in either dental plaque, on the dorsum of the tongue, or on keratinized gingiva.
“Many microbial subtypes are specialized to reside in either dental plaque, on the dorsum of the tongue, or on keratinized gingiva.234”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [234]
Site specialization is dictated by the ability of a microbe to adhere, colonize, grow, and divide at that site.
“Site specialization is dictated by the ability of a microbe to adhere, colonize, grow, and divide at that site.227, 234”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [234]
Most microbes in the mouth demonstrate site specialization.
“However, most microbes in the mouth demonstrate site specialization.”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [234]
Some species, such as S mitis, H parainfluenzae, and Porphyromonas pasteri do not demonstrate site specialization and are found in a variety of habitats.
“Alternatively, some species, such as S mitis, H parainfluenzae, and Porphyromonas pasteri do not demonstrate site specialization and are found in a variety of habitats.”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [234]
Up to 80% of oral bacteria are dominated by about 200 species in the Phyla Firmicutes and Proteobacteria, with contributions from Bacteroidetes, Actinobacteria and Fusobacteria totaling upwards of 95% of all identified oral microbiota.
“Up to 80% of oral bacteria are dominated by about 200 species in the Phyla Firmicutes (esp. Streptococcus, Veillonella, Granulicatella, Gemella spp.) and Proteobacteria (esp. Neisseria, Haemophilus spp.), with contributions from Bacteroidetes, Actinobacteria and Fusobacteria totaling upwards of 95% of all identified oral microbiota (Figure 2)[171–177].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [174]
Further diversity exists between the varied micro-ecologies of the mouth, such as the tooth surface, gingiva, hard and soft palate, and even regionally on the tongue.
“Further diversity exists between the varied micro-ecologies of the mouth[174,178], such as the tooth surface, gingiva, hard and soft palate, and even regionally on the tongue (Figure 2)[173,176,179].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [174]
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Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,706 · see citing works
Basic local alignment search tool
Altschul, S. F., Gish, W., Miller, W., Myers, E. W., & Lipman, D. J. (1990) · Journal of Molecular Biology · doi:10.1006/jmbi.1990.9999 · Cited by 98,669 · see citing works
A Mathematical Theory of Communication
Shannon, C. E. (1948) · Bell System Technical Journal · doi:10.1002/j.1538-7305.1948.tb01338.x · Cited by 88,486 · see citing works
vegan: Community Ecology Package
Oksanen, J., Simpson, G. L., Blanchet, F. G., Kindt, R., Legendre, P., Minchin, P. R., O’Hara, R. B., Sólymos, P., Stevens, M. H. H., Szöcs, E., et al. (2001) · doi:10.32614/cran.package.vegan · Cited by 27,099 · see citing works
Naive Bayesian Classifier for Rapid Assignment of rRNA Sequences into the New Bacterial Taxonomy
Wang, Q., Garrity, G. M., Tiedje, J. M., & Cole, J. R. (2007) · Applied and Environmental Microbiology · doi:10.1128/aem.00062-07 · Cited by 19,770 · see citing works
Metagenomic biomarker discovery and explanation
Segata, N., Izard, J., Waldron, L., Gevers, D., Miropolsky, L., Garrett, W. S., & Huttenhower, C. (2011) · Genome Biology · doi:10.1186/gb-2011-12-6-r60 · Cited by 16,192 · see citing works
ggplot2: Elegant Graphics for Data Analysis
Wickham, H. (2009) · doi:10.1007/978-0-387-98141-3 · Cited by 14,447 · see citing works
Structure, function and diversity of the healthy human microbiome
The Human Microbiome Project Consortium (2012) · Nature · doi:10.1038/nature11234 · Cited by 11,726 · see citing works
McDonald, D. T., Price, M. N., Goodrich, J. K., Nawrocki, E. P., DeSantis, T. Z., Probst, A. J., Andersen, G. L., Knight, R. D., & Hugenholtz, P. (2011) · The ISME Journal · doi:10.1038/ismej.2011.139 · Cited by 5,010 · see citing works
PyNAST: a flexible tool for aligning sequences to a template alignment
Caporaso, J. G., Bittinger, K. L., Bushman, F. D., DeSantis, T. Z., Andersen, G. L., & Knight, R. D. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp636 · Cited by 3,374 · see citing works
Dewhirst, F. E., Chen, T., Izard, J., Paster, B. J., Tanner, A. C. R., Yu, W.-H., Lakshmanan, A., & Wade, W. G. (2010) · Journal of Bacteriology · doi:10.1128/jb.00542-10 · Cited by 3,352 · see citing works
Defining the normal bacterial flora of the oral cavity
Aas, J. A., Paster, B. J., Stokes, L. N., Olsen, I., & Dewhirst, F. E. (2005) · Journal of Clinical Microbiology · doi:10.1128/jcm.43.11.5721-5732.2005 · Cited by 3,092 · see citing works
A framework for human microbiome research
The Human Microbiome Project Consortium (2012) · Nature · doi:10.1038/nature11209 · Cited by 2,650 · see citing works
Socransky, S. S., & Haffajee, A. D. (2005) · Periodontology 2000 · doi:10.1111/j.1600-0757.2005.00107.x · Cited by 1,691 · see citing works
Defining the healthy “core microbiome” of oral microbial communities
Zaura, E., Keijser, B. J., Huse, S. M., & Crielaard, W. (2009) · BMC Microbiology · doi:10.1186/1471-2180-9-259 · Cited by 1,323 · see citing works
Self-citationAccuracy and quality of massively parallel DNA pyrosequencing
Huse, S. M., Huber, J. A., Morrison, H. G., Sogin, M. L., & Welch, D. B. M. (2007) · Genome biology · doi:10.1186/gb-2007-8-7-r143 · Cited by 1,285 · see citing works
Self-citationSegata, N., Haake, S. K., Mannon, P., Lemon, K. P., Waldron, L., Gevers, D., Huttenhower, C., & Izard, J. (2012) · Genome Biology · doi:10.1186/gb-2012-13-6-r42 · Cited by 1,076 · see citing works
Pyrosequencing analysis of the oral microflora of healthy adults
Keijser, B. J. F., Zaura, E., Huse, S. M., van der Vossen, J. M. B. M., Schuren, F. H. J., Montijn, R. C., ten Cate, J. M., & Crielaard, W. (2008) · Journal of Dental Research · doi:10.1177/154405910808701104 · Cited by 669 · see citing works
Bacterial diversity in the oral cavity of 10 healthy individuals
Bik, E. M., Long, C. D., Armitage, G. C., Loomer, P., Emerson, J., Mongodin, E. F., Nelson, K. E., Gill, S. R., Fraser-Liggett, C. M., & Relman, D. A. (2010) · The ISME Journal · doi:10.1038/ismej.2010.30 · Cited by 651 · see citing works
Oligotyping: differentiating between closely related microbial taxa using 16S rRNA gene data
Eren, A. M., Maignien, L., Sul, W. J., Murphy, L. G., Grim, S. L., Morrison, H. G., & Sogin, M. L. (2013) · Methods in Ecology and Evolution · doi:10.1111/2041-210x.12114 · Cited by 620 · see citing works
Self-citationA Natural View of Microbial Biodiversity within Hot Spring Cyanobacterial Mat Communities
Ward, D. M., Ferris, M. J., Nold, S. C., & Bateson, M. M. (1998) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.62.4.1353-1370.1998 · Cited by 583 · see citing works
A Core Human Microbiome as Viewed through 16S rRNA Sequence Clusters
Huse, S. M., Ye, Y., Zhou, Y., & Fodor, A. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034242 · Cited by 572 · see citing works
Self-citationKAWAMURA, Y., Hou, X.-G., Sultana, F., MIURA, H., & EZAKI, T. (1995) · International Journal of Systematic Bacteriology · doi:10.1099/00207713-45-2-406 · Cited by 502 · see citing works
Distribution of selected bacterial species on intraoral surfaces
Mager, D. L., Ximenez‐Fyvie, L., Haffajee, A. D., & Socransky, S. S. (2003) · Journal Of Clinical Periodontology · doi:10.1034/j.1600-051x.2003.00376.x · Cited by 481 · see citing works
Aagaard, K., Petrosino, J., Keitel, W., Watson, M., Katancik, J., Garcia, N., Patel, S., Cutting, M., Madden, T., Hamilton, H., et al. (2013) · The FASEB Journal · doi:10.1096/fj.12-220806 · Cited by 383 · see citing works
Accuracy and quality assessment of 454 GS-FLX Titanium pyrosequencing
Gilles, A., Meglécz, E., Pech, N., Ferreira, S., Malausa, T., & Martin, J. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-245 · Cited by 377 · see citing works
Genotypic Diversity Within a Natural Coastal Bacterioplankton Population
Thompson, J. R., Preheim, S. P., Pharino, C., Klepac‐Ceraj, V., Hunt, D. E., Benoit, J., Sarma-Rupavtarm, R. B., Distel, D. L., & Polz, M. F. (2005) · Science · doi:10.1126/science.1106028 · Cited by 360 · see citing works
Maignien, L., DeForce, E., Chafee, M. E., et al. (2014) · mBio · doi:10.1128/mbio.00682-13 · Cited by 315 · see citing works
Metagenomic study of the oral microbiota by Illumina high-throughput sequencing
Lazarević, V., Whiteson, K., Huse, S. M., Hernández, D., Farinelli, L., Østerås, M., Schrenzel, J., & François, P. (2009) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2009.09.012 · Cited by 313 · see citing works
Self-citationHost-specificity among abundant and rare taxa in the sponge microbiome
Réveillaud, J., Maignien, L., Eren, A. M., et al. (2014) · The ISME Journal · doi:10.1038/ismej.2013.227 · Cited by 261 · see citing works
Self-citationEren, A. M., Zozaya, M., Taylor, C. M., Dowd, S. E., Martin, D. H., & Ferris, M. J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026732 · Cited by 222 · see citing works
Self-citationSpecies-level classification of the vaginal microbiome
Fettweis, J. M., Serrano, M. G., Sheth, N. U., Mayer, C. M., Glascock, A. L., Brooks, J. P., Jefferson, K. K., & Buck, G. A. (2012) · BMC Genomics · doi:10.1186/1471-2164-13-s8-s17 · Cited by 187 · see citing works
Species-Level Analysis of DNA Sequence Data from the NIH Human Microbiome Project
Conlan, S., Kong, H. H., & Segre, J. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047075 · Cited by 175 · see citing works
Jensen, A., Fagö-Olsen, H., Sørensen, C. H., & Kilian, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056418 · Cited by 156 · see citing works
The Genome of Streptococcus mitis B6 - What Is a Commensal?
Denapaite, D., Brückner, R., Nuhn, M., Reichmann, P., Henrich, B., Maurer, P., Schähle, Y., Selbmann, P., Zimmermann, W., Wambutt, R., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009426 · Cited by 116 · see citing works
Sewage reflects the distribution of human faecal L achnospiraceae
McLellan, S. L., Newton, R. J., VandeWalle, J. L., Shanks, O. C., Huse, S. M., Eren, A. M., & Sogin, M. L. (2013) · Environmental Microbiology · doi:10.1111/1462-2920.12092 · Cited by 109 · see citing works
Self-citationShao, W., Boltz, V. F., Spindler, J., et al. (2013) · Retrovirology · doi:10.1186/1742-4690-10-18 · Cited by 94 · see citing works
Possible role of the anaerobe in tonsillitis.
Reilly, S., Timmis, P., Beeden, A. G., et al. (1981) · Journal of Clinical Pathology · doi:10.1136/jcp.34.5.542 · Cited by 71 · see citing works
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Callahan, B. J., McMurdie, P. J., Rosen, M. J., Han, A. W., Johnson, A. J. A., & Holmes, S. P. (2016) · Nature Methods · doi:10.1038/nmeth.3869 · Cited by 35,698 · see citing works
Davis, N. M., Proctor, D. M., Holmes, S. P., Relman, D. A., & Callahan, B. J. (2018) · Microbiome · doi:10.1186/s40168-018-0605-2 · Cited by 3,493 · see citing works
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Mark Welch, J. L., Rossetti, B. J., Rieken, C. W., Dewhirst, F. E., & Borisy, G. G. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1522149113 · Cited by 968 · see citing works
Self-citationOral microbiomes: more and more importance in oral cavity and whole body
Gao, L., Xu, T., Huang, G., Jiang, S., Gu, Y., & Chen, F. (2018) · Protein & Cell · doi:10.1007/s13238-018-0548-1 · Cited by 770 · see citing works
The oral microbiome: Role of key organisms and complex networks in oral health and disease
Sedghi, L., DiMassa, V., Harrington, A., Lynch, S. V., & Kapila, Y. L. (2021) · Periodontology 2000 · doi:10.1111/prd.12393 · Cited by 755 · see citing works
Prevotella Diversity, Niches and Interactions with the Human Host
Tett, A., Pasolli, E., Masetti, G., Ercolini, D., & Segata, N. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-021-00559-y · Cited by 748 · see citing works
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Van Rossum, T., Ferretti, P., Maistrenko, O. M., & Bork, P. (2020) · Nature Reviews Microbiology · doi:10.1038/s41579-020-0368-1 · Cited by 441 · see citing works
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Chen, L.-X., Anantharaman, K., Shaiber, A., Eren, A. M., & Banfield, J. F. (2020) · Genome Research · doi:10.1101/gr.258640.119 · Cited by 401 · see citing works
Self-citationGacias, M., Gaspari, S., Santos, P.-M. G., Tamburini, S., Andrade, M., Zhang, F., Shen, N., Tolstikov, V., Kiebish, M. A., Dupree, J. L., et al. (2016) · eLife · doi:10.7554/elife.13442 · Cited by 308 · see citing works
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Newton, R. J., McLellan, S. L., Dila, D. K., Vineis, J. H., Morrison, H. G., Eren, A. M., & Sogin, M. L. (2015) · mBio · doi:10.1128/mbio.02574-14 · Cited by 299 · see citing works
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Sterzenbach, T., Helbig, R., Hannig, C., & Hannig, M. (2020) · Clinical Oral Investigations · doi:10.1007/s00784-020-03646-1 · Cited by 212 · see citing works
Nagata, N., Nishijima, S., Miyoshi-Akiyama, T., Kojima, Y., Kimura, M., Aoki, R., Ohsugi, M., Ueki, K., Miki, K., Iwata, E., et al. (2022) · Gastroenterology · doi:10.1053/j.gastro.2022.06.070 · Cited by 178 · see citing works
Koch, C. D., Gladwin, M. T., Freeman, B. A., Lundberg, J. O., Weitzberg, E., & Morris, A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.015 · Cited by 186 · see citing works
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De Filippis, F., Vannini, L., La Storia, A., Laghi, L., Piombino, P., Stellato, G., Serrazanetti, D. I., Gozzi, G., Turroni, S., Ferrocino, I., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0112373 · Cited by 146 · see citing works
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Asakawa, M., Takeshita, T., Furuta, M., Kageyama, S., Takeuchi, K., Hata, J., Ninomiya, T., & Yamashita, Y. (2018) · mSphere · doi:10.1128/msphere.00332-18 · Cited by 113 · see citing works
- Authors
- Eren, A. M., Borisy, G. G., Huse, S. M., & Mark Welch, J. L.
- Affiliations
- Marine Biological Laboratory (US)
- The Forsyth Institute (US)
- Brown University (US)
- Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory, Woods Hole, MA 02543;
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-06-25
- Volume
- 111
- Issue
- 28
- Pages
- E2875-84
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4104879
- OpenAlex
- W1565875270
- Cited by
- 347
- References
- 38
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 29 · 2023: 31 · 2022: 28 · 2021: 31 · 2020: 36 · 2019: 44 · 2018: 34 · 2017: 26 · 2016: 23 · 2015: 19 · 2014: 8
- FWCI
- 33.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (UH2DK083993, UH3DK083993, DK083993)
- National Institute of Dental and Craniofacial Research (DE 022586, R01DE022586)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- oligotyping, oral microbiota, 16S rRNA gene, Shannon entropy, taxonomic resolution, dental plaque, gingiva, buccal mucosa, microbial diversity, Human Microbiome Project
- MeSH terms
- Adolescent, Adult, Bacteria, Female, Genes, Bacterial, Humans, Male, Mouth Mucosa, RNA, Bacterial, RNA, Ribosomal, 16S, Genes, rRNA, Databases, Nucleic Acid, Microbiota
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