Understanding the evolutionary history of microbial communities within the human body (microbiota) will provide key insights into the origins of numerous modern‐day diseases. Ancient microbial DNA preserved in calcified dental plaque (calculus) now provides an opportunity to reconstruct past oral microbiota and examine how these microbes are linked with health and disease through time. We use High Throughput Sequencing to obtain ancient and modern microbial DNA from dental calculus on four continents over the past 48,000 years, reconstructing distinct oral microbiota evolutionary histories at each location. Highly resolved microbiota histories in Europe suggest that local environments, adoption of different diets, interbreeding with other hominids, and exposure to the Industrial Revolution are key drivers of microbiota shifts over time and likely underpin both oral and chronic disease origins. On other continents, oral microbial communities were distinct from those in Europe, highlighting the need to include diverse populations in evolutionary reconstructions. For example, South American oral microbiota was influenced by corn utilization and adaptation to specific environments (i.e., high altitude vs coastal) and contained distinct species linked with oral disease. As microbiota histories in each location are distinct, we theorize that they play distinct roles in the development of disease, both oral and systemic, across different populations, with profound implications for the Indigenous health gap. Together, these data provide the first glimpse of global human microbiota evolution in real‐time and provide the foundation to understand why certain bacterial communities are now linked to disease in a modern world.
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