title: Pathogens and host immunity in the ancient human oral cavity.
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.
authors.affiliation: 1] Centre for Evolutionary Medicine, Institute of Anatomy, University of Zürich, Zürich, Switzerland. [2] Department of Anthropology, University of Oklahoma, Norman, Oklahoma, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Warinner
authors.affiliation: 1] Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland. [2] Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: João F Matias
authors.initials: JF
authors.lastname: Rodrigues
authors.affiliation: 1] Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland. [2] Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Rounak
authors.initials: R
authors.lastname: Vyas
authors.affiliation: Functional Genomics Center Zürich, University of Zürich/Swiss Federal Institute of Technology (ETH) Zürich, Zürich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Trachsel
authors.affiliation: Centre for Evolutionary Medicine, Institute of Anatomy, University of Zürich, Zürich, Switzerland.
authors.forename: Natallia
authors.initials: N
authors.lastname: Shved
authors.affiliation: Functional Genomics Center Zürich, University of Zürich/Swiss Federal Institute of Technology (ETH) Zürich, Zürich, Switzerland.
authors.forename: Jonas
authors.initials: J
authors.lastname: Grossmann
authors.affiliation: 1] BioArCh, Department of Archaeology, University of York, York, UK. [2] University of Leicester Archaeological Services (ULAS), School of Archaeology and Ancient History, University of Leicester, Leicester, UK.
authors.forename: Anita
authors.initials: A
authors.lastname: Radini
authors.affiliation: Department of Physics, University of York, York, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Hancock
authors.affiliation: Department of Anthropology, University of Oklahoma, Norman, Oklahoma, USA.
authors.forename: Raul Y
authors.initials: RY
authors.lastname: Tito
authors.affiliation: BioArCh, Department of Archaeology, University of York, York, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Fiddyment
authors.affiliation: BioArCh, Department of Archaeology, University of York, York, UK.
authors.forename: Camilla
authors.initials: C
authors.lastname: Speller
authors.affiliation: BioArCh, Department of Archaeology, University of York, York, UK.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hendy
authors.affiliation: BioArCh, Department of Archaeology, University of York, York, UK.
authors.forename: Sophy
authors.initials: S
authors.lastname: Charlton
authors.affiliation: Centre of Dental Medicine, Institute of Oral Biology, University of Zürich, Zürich, Switzerland.
authors.forename: Hans Ulrich
authors.initials: HU
authors.lastname: Luder
authors.affiliation: 1] Research Group on Plant Foods in Hominin Dietary Ecology, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. [2] Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. [3] Department of Prehistory and Archaeology, University of Valencia, Valencia, Spain.
authors.forename: Domingo C
authors.initials: DC
authors.lastname: Salazar-García
authors.affiliation: 1] Research Group Neuro-Endocrine-Immune Interactions, Institute of Anatomy, University of Zürich, Zürich, Switzerland. [2] Zürich Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Eppler
authors.affiliation: Centre for Evolutionary Medicine, Institute of Anatomy, University of Zürich, Zürich, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Seiler
authors.affiliation: 1] Department of Biology, Microbiology, University of Copenhagen, Copenhagen, Denmark. [2] Department of Environmental Science, Aarhus Universitet, Roskilde, Denmark.
authors.forename: Lars H
authors.initials: LH
authors.lastname: Hansen
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.
authors.forename: José Alfredo Samaniego
authors.initials: JA
authors.lastname: Castruita
authors.affiliation: Functional Genomics Center Zürich, University of Zürich/Swiss Federal Institute of Technology (ETH) Zürich, Zürich, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Barkow-Oesterreicher
authors.affiliation: BioArCh, Department of Archaeology, University of York, York, UK.
authors.forename: Kai Yik
authors.initials: KY
authors.lastname: Teoh
authors.affiliation: Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christian D
authors.initials: CD
authors.lastname: Kelstrup
authors.affiliation: Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jesper V
authors.initials: JV
authors.lastname: Olsen
authors.affiliation: Functional Genomics Center Zürich, University of Zürich/Swiss Federal Institute of Technology (ETH) Zürich, Zürich, Switzerland.
authors.forename: Paolo
authors.initials: P
authors.lastname: Nanni
authors.affiliation: 1] Department of Immunology and Infectious Diseases, Forsyth Institute, Cambridge, Massachusetts, USA. [2] Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, Massachusetts, USA.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Kawai
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Eske
authors.initials: E
authors.lastname: Willerslev
authors.affiliation: 1] Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland. [2] Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors.forename: Christian
authors.identifier: 0000000177349102
authors.initials: C
authors.lastname: von Mering
authors.affiliation: Department of Anthropology, University of Oklahoma, Norman, Oklahoma, USA.
authors.forename: Cecil M
authors.initials: CM
authors.lastname: Lewis
authors.affiliation: BioArCh, Department of Archaeology, University of York, York, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Collins
authors.affiliation: 1] Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark. [2] Ancient DNA Laboratory, Murdoch University, Perth, Western Australia, Australia.
authors.forename: M Thomas P
authors.initials: MT
authors.lastname: Gilbert
authors.affiliation: 1] Centre for Evolutionary Medicine, Institute of Anatomy, University of Zürich, Zürich, Switzerland. [2].
authors.forename: Frank
authors.initials: F
authors.lastname: Rühli
authors.affiliation: 1] Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark. [2].
authors.forename: Enrico
authors.identifier: 0000000178857811
authors.initials: E
authors.lastname: Cappellini
mesh_terms: D001106:Archaeology; D041963:Bacteroidetes / Q000235:genetics*; D001483:Base Sequence; D003728:Dental Calculus / Q000266:history / Q000382:microbiology*; D005504:Food Analysis; D016680:Genome, Bacterial / Q000235:genetics*; D005858:Germany; D049691:History, Medieval; D006801:Humans; D064307:Microbiota / Q000235:genetics*; D008969:Molecular Sequence Data; D009055:Mouth / Q000276:immunology / Q000382:microbiology*; D010802:Phylogeny; D020543:Proteome / Q000235:genetics*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D053719:Tandem Mass Spectrometry
chemical_list: D020543:Proteome; D012336:RNA, Ribosomal, 16S