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Pathogens and host immunity in the ancient human oral cavity

Nature Genetics volume 46, pages 336–344 (2014)Cite this article

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Abstract

Calcified dental plaque (dental calculus) preserves for millennia and entraps biomolecules from all domains of life and viruses. We report the first, to our knowledge, high-resolution taxonomic and protein functional characterization of the ancient oral microbiome and demonstrate that the oral cavity has long served as a reservoir for bacteria implicated in both local and systemic disease. We characterize (i) the ancient oral microbiome in a diseased state, (ii) 40 opportunistic pathogens, (iii) ancient human–associated putative antibiotic resistance genes, (iv) a genome reconstruction of the periodontal pathogen Tannerella forsythia, (v) 239 bacterial and 43 human proteins, allowing confirmation of a long-term association between host immune factors, 'red complex' pathogens and periodontal disease, and (vi) DNA sequences matching dietary sources. Directly datable and nearly ubiquitous, dental calculus permits the simultaneous investigation of pathogen activity, host immunity and diet, thereby extending direct investigation of common diseases into the human evolutionary past.

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Figure 1: Taxonomic and phylogenetic characterization of ancient dental calculus.
Figure 2: Genomic coverage plot for the periodontal pathogen T. forsythia, with details of gene and protein coverage of the virulence factor TF2663, tfsB, from medieval human dental calculus (G12).
Figure 3: Metaproteomic comparison of human proteins in modern and ancient dental samples.
Figure 4: Genetic, microfossil, zooarchaeological and stable isotopic evidence for the medieval human diet at Dalheim, Germany.
Figure 5: Evidence of microscopic and biomolecular preservation of ancient dental calculus.

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Proteomics Identifications Database

Sequence Read Archive

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Acknowledgements

We thank the Kantonale Ethik-Kommission Zürich, the Functional Genomics Center Zürich, the Center for Microscopy and Image Analysis, and the Institute of Oral Biology at the University of Zürich; the PRIDE Team; G. Akgül, K. Alt, D. Ashford, P. Ashton, H. Barton, A. Bouwman, C. Burger, D. Coulthard, J. Hublin, V. Meskenaite, F. Najar, M. Richards, K. Sankaranarayanan, R. Schlapbach, L. Shillito, T. Stöllner, O. Ullrich and H. Zbinden for assistance with data collection, analysis and management; and M. Carver, F. Dewhirst, A. Tanner, K. Hardy and A. Henry for helpful comments on early drafts and data analyses. This work was supported by the Mäxi Foundation Zürich, the Swiss Foundation for Nutritional Research, Danish Research Foundation grant 29396, Danish Council for Independent Research grant 10-081390, Lundbeck Foundation grants R52-A5062 and R44-A4384, US National Institutes of Health grants R01-HG005172, R01-GM089886, R01-DE018499 and R21-DE018310, European Research Council grant UMICIS/242870, Marie Curie grants EUROTAST FP7-PEOPLE-2010 MC ITN, PALIMPSEST FP7-PEOPLE-2011-IEF 299101 and ORCA FP7-PEOPLE-2011-IOF 299075, a C2D2 Research Priming Fund grant partly funded by Wellcome Trust 097829, Swiss National Science Foundation grant 31003A-135688, the Novartis Foundation, the Novo Nordisk Foundation, the Max Planck Society and the University of York.

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Author notes

  1. Frank Rühli and Enrico Cappellini: These authors jointly directed this work.

Authors and Affiliations

  1. Centre for Evolutionary Medicine, Institute of Anatomy, University of Zürich, Zürich, Switzerland

    Christina Warinner, Natallia Shved, Roger Seiler & Frank Rühli

  2. Department of Anthropology, University of Oklahoma, Norman, Oklahoma, USA

    Christina Warinner, Raul Y Tito & Cecil M Lewis Jr

  3. Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland

    João F Matias Rodrigues, Rounak Vyas & Christian von Mering

  4. Swiss Institute of Bioinformatics, Lausanne, Switzerland

    João F Matias Rodrigues, Rounak Vyas & Christian von Mering

  5. Functional Genomics Center Zürich, University of Zürich/Swiss Federal Institute of Technology (ETH) Zürich, Zürich, Switzerland

    Christian Trachsel, Jonas Grossmann, Simon Barkow-Oesterreicher & Paolo Nanni

  6. Department of Archaeology, BioArCh, University of York, York, UK

    Anita Radini, Sarah Fiddyment, Camilla Speller, Jessica Hendy, Sophy Charlton, Kai Yik Teoh & Matthew J Collins

  7. University of Leicester Archaeological Services (ULAS), School of Archaeology and Ancient History, University of Leicester, Leicester, UK

    Anita Radini

  8. Department of Physics, University of York, York, UK

    Y Hancock

  9. Centre of Dental Medicine, Institute of Oral Biology, University of Zürich, Zürich, Switzerland

    Hans Ulrich Luder

  10. Research Group on Plant Foods in Hominin Dietary Ecology, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany

    Domingo C Salazar-García

  11. Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany

    Domingo C Salazar-García

  12. Department of Prehistory and Archaeology, University of Valencia, Valencia, Spain

    Domingo C Salazar-García

  13. Research Group Neuro-Endocrine-Immune Interactions, Institute of Anatomy, University of Zürich, Zürich, Switzerland

    Elisabeth Eppler

  14. Zürich Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland

    Elisabeth Eppler

  15. Department of Biology, Microbiology, University of Copenhagen, Copenhagen, Denmark

    Lars H Hansen

  16. Department of Environmental Science, Aarhus Universitet, Roskilde, Denmark

    Lars H Hansen

  17. Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark

    José Alfredo Samaniego Castruita, Eske Willerslev, M Thomas P Gilbert & Enrico Cappellini

  18. Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Christian D Kelstrup & Jesper V Olsen

  19. Department of Immunology and Infectious Diseases, Forsyth Institute, Cambridge, Massachusetts, USA

    Toshihisa Kawai

  20. Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, Massachusetts, USA

    Toshihisa Kawai

  21. Ancient DNA Laboratory, Murdoch University, Perth, Western Australia, Australia

    M Thomas P Gilbert

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  1. Christina Warinner
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Contributions

C.W. conceived the project, with input from M.J.C. R.S. and F.R. contributed samples. C.W., E.C., M.J.C., M.T.P.G., C.v.M., A.R. and Y.H. designed the experiments. C.W., E.C., N.S., C.T., A.R., Y.H., D.C.S.-G., S.C., S.F., H.U.L., P.N., C.D.K., J.V.O., K.Y.T. and E.E. performed the experiments. J.F.M.R., R.V., C.W., C.v.M., J.G., A.R., Y.H., R.Y.T., S.F., C.S., S.C., D.C.S.-G., J.H., J.A.S.C., L.H.H. and T.K. analyzed the data. S.B.-O., Y.H., E.W., C.M.L., M.T.P.G., M.J.C. and F.R. contributed material support to the project. Y.H. wrote the supplementary Raman section. C.W. wrote the manuscript, with critical input from C.M.L., M.T.P.G., M.J.C., C.v.M., E.W., E.C. and the remaining authors.

Corresponding authors

Correspondence to Christina Warinner or Enrico Cappellini.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–23, Supplementary Tables 1 and 5–29, and Supplementary Note (PDF 11364 kb)

Supplementary Table 2

Comparison of putative pathogens identified in ancient dental calculus and HMP healthy cohort dental plaque samples. (XLSX 124 kb)

Supplementary Table 3

Specific virulence factors and mobile elements identified within ancient dental calculus metagenomic and metaproteomic data. (XLSX 4997 kb)

Supplementary Table 4

Putative antibiotic resistance genes identified from ancient dental calculus metagenomic data. (XLS 185 kb)

Supplementary Data Set 1

Ancient dental samples BIOM file for 454 data. (TXT 449 kb)

Supplementary Data Set 2

Ancient dental and HMP samples BIOM file for 454 data. (TXT 7461 kb)

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Warinner, C., Rodrigues, J., Vyas, R. et al. Pathogens and host immunity in the ancient human oral cavity. Nat Genet 46, 336–344 (2014). https://doi.org/10.1038/ng.2906

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