Pathogens and host immunity in the ancient human oral cavity

Christina Warinner, João F Matias Rodrigues, Rounak Vyas, Christian Trachsel, Natallia Shved, Jonas Grossmann, Anita Radini, Y Hancock, Raul Y Tito, Sarah Fiddyment, Camilla Speller, Jessica Hendy, Sophy Charlton, Hans Ulrich Luder, Domingo C Salazar-García, Elisabeth Eppler, Roger Seiler, Lars H Hansen, José Alfredo Samaniego Castruita, Simon Barkow-Oesterreicher, Kai Yik Teoh, Christian D Kelstrup, Jesper V Olsen, Paolo Nanni, Toshihisa Kawai, Eske Willerslev, Christian von Mering, Cecil M Lewis, Matthew J Collins, M Thomas P Gilbert, Frank Rühli, Enrico Cappellini

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.