The oral microbiome plays key roles in human biology, health, and disease, but little is known about the global diversity, variation, or evolution of this microbial community. To better understand the evolution and changing ecology of the human oral microbiome, we analyzed 124 dental biofilm metagenomes from humans, including Neanderthals and Late Pleistocene to present-day modern humans, chimpanzees, and gorillas, as well as New World howler monkeys for comparison. We find that a core microbiome of primarily biofilm structural taxa has been maintained throughout African hominid evolution, and these microbial groups are also shared with howler monkeys, suggesting that they have been important oral members since before the catarrhine-platyrrhine split ca. 40 Mya. However, community structure and individual microbial phylogenies do not closely reflect host relationships, and the dental biofilms of Homo and chimpanzees are distinguished by major taxonomic and functional differences. Reconstructing oral metagenomes from up to 100 thousand years ago, we show that the microbial profiles of both Neanderthals and modern humans are highly similar, sharing functional adaptations in nutrient metabolism. These include an apparent Homo-specific acquisition of salivary amylase-binding capability by oral streptococci, suggesting microbial coadaptation with host diet. We additionally find evidence of shared genetic diversity in the oral bacteria of Neanderthal and Upper Paleolithic modern humans that is not observed in later modern human populations. Differences in the oral microbiomes of African hominids provide insights into human evolution, the ancestral state of the human microbiome, and a temporal framework for understanding microbial health and disease.

Animal Ecology Department of Ecology and Genetics Uppsala University 75236 Uppsala Sweden

Anthropology Program California State University Channel Islands Camarillo CA 93012

Berliner Gesellschaft für Anthropologie Ethnologie und Urgeschichte 10117 Berlin Germany

Centre for Human Evolution Research The Natural History Museum London SW7 5BD United Kingdom

Centre for Palaeogenetics 10691 Stockholm Sweden

Clínica Alboraya 10 46010 València Spain

Clínica Dental Grande Mateu 46004 València Spain

De la Préhistoire à l'Actuel Culture Environnement et Anthropologie CNRS UMR 5199 Université de Bordeaux 33615 Pessac France

Departament de Prehistòria Historia i Arqueología Universitat de València 46010 València Spain

Departamento de Prehistòria y Arqueología Universidad Nacional de Educación 28040 Madrid Spain

Departamento de Zoología y Antropología Física Universidad de Murcia 30100 Murcia Spain

Department of Anthropology California State University Northridge CA 91330

Department of Anthropology Harvard University Cambridge MA 02138

Department of Anthropology Masaryk University 61137 Brno Czech Republic

Department of Anthropology University of New Mexico Albuquerque NM 87131

Department of Anthropology University of Oklahoma Norman OK 73019

Department of Anthropology University of South Florida St Petersburg FL 33701

Department of Anthropology University of Winnipeg Winnipeg MB R3T 3C7 Canada

Department of Anthropology Western University London ON N6A 5C2 Canada

Department of Archaeogenetics Max Planck Institute for Evolutionary Anthropology 04103 Leipzig Germany

Department of Archaeogenetics Max Planck Institute for the Science of Human History 07745 Jena Germany

Department of Archaeogenetics Max Planck Institute for the Science of Human History 07745 Jena Germany;

Department of Archaeology Faculty of Philosophy University of Belgrade 11000 Belgrade Serbia

Department of Archaeology Max Planck Institute for the Science of Human History 07745 Jena Germany

Department of Bioinformatics and Genetics Swedish Museum of Natural History 10405 Stockholm Sweden

Department of Geological Sciences University of Cape Town Rondebosch 7701 South Africa

Department of Human Evolution Max Planck Institute for Evolutionary Anthropology 04103 Leipzig Germany

Department of Human Evolutionary Biology Harvard University Cambridge MA 02138

Department of Humanities University of Ferrara 44121 Ferrara Italy

Department of Microbiology and Plant Biology University of Oklahoma Norman OK 73019

Department of Microbiology Immunology and Genetics University of North Texas Health Science Center Fort Worth TX 76107

Department of Microbiology The Forsyth Institute Cambridge MA 02142

Deutsche Forschungsgemeinschaft Centre for Advanced Studies Words Bones Genes Tools Eberhard Karls University of Tübingen 72070 Tübingen Germany

Division of Clinical Anatomy and Biological Anthropology Department of Human Biology University of Cape Town Cape Town 7925 South Africa

Escribano Escrivá Clínica Dental 38003 Santa Cruz de Tenerife Spain

Faculty of Archaeology Leiden University 2333CC Leiden The Netherlands

Grupo de Investigación en Prehistòria IT 1223 19 Ikerbasque Basque Foundation for Science 01006 Vitoria Gasteiz Spain

Institut für Ur und Frühgeschichte und Archäologie des Mittelalters Eberhard Karls University of Tübingen 72074 Tübingen Germany

Institute for Archaeological Sciences Eberhard Karls University of Tübingen 72070 Tübingen Germany

Institute for Pre and Protohistoric Archaeology and Archaeology of the Roman Provinces Ludwig Maximilians University Münich 80539 Münich Germany

Institute of Archaeology at Brno Czech Academy of Sciences 60200 Brno Czech Republic

Institute of Environmental Geology and Geoengineering National Research Council Milano Lombardia 20126 Italy

Instituto Internacional de Investigaciones Prehistóricas de Cantabria Universidad de Cantabria Gobierno de Cantabria Banco 39071 Santander Spain

Laboratoire Chronoenvironnement CNRS UMR 6249 25030 Besançon France

Laboratories of Molecular Anthropology and Microbiome Research University of Oklahoma Norman OK 73019

Landesamt für Denkmalpflege im Regierungspräsidium Stuttgart 78467 Konstanz Germany

McDonald Institute for Archaeological Research University of Cambridge Cambridge CB2 3ER United Kingdom

Museum für Vor und Frühgeschichte Berlin Stiftung Preussischer Kulturbesitz 10117 Berlin Germany

Natural History Museum University of Oslo 0562 Oslo Norway

Oral Medicine Infection and Immunity Harvard School of Dental Medicine Boston MA 02115

Palaeobiology Biogeology Department of Geosciences Eberhard Karls University of Tübingen 72074 Tübingen Germany

Paleoanthropology Institute of Archaeological Sciences Eberhard Karls University of Tübingen 72070 Tübingen Germany

Prehistoria Departamento de Historia Geografía y Comunicación Universidad de Burgos 09001 Burgos Spain

School of Human Evolution and Social Change Arizona State University Tempe AZ 85287

Science for Life Laboratory 75237 Uppsala Sweden

Senckenberg Centre for Human Evolution and Palaeoenviroment Eberhard Karls University of Tübingen 72074 Tübingen Germany

Service Régional d'Archéologie de Bourgogne Franche Comté Direction Régionale des Affaires Culturelles Bourgogne Franche Comté 25043 Besançon France

Sonderforschungsbereiche 1070 Ressourcen Kulturen Eberhard Karls University of Tübingen 72074 Tübingen Germany

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Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):e2110764118. doi: 10.1073/pnas.2110764118. PubMed

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