Ancient and Contemporary Analyses of the Impact of the Agricultural Transition on the Human Oral Microbiome

Abstract

Communities of bacteria inhabit different parts of the human body and influence human metabolic, immune and even nervous systems, playing key roles in human health and disease. This microbial world and its genomes were recently discovered and was termed the "microbiome”. Recent research suggests that human cultural changes such as the human transition to agriculture and the subsequent Industrial revolution changed the human microbiome. These changes may underpin many modern metabolic diseases, such as diabetes and heart disease, and explain why modern metabolic disease is more prevalent in humans not currently living a hunter-gatherer lifestyle. However, limited geographical sampling has resulted in an incomplete understanding of the impact of these human cultural changes on the microbiome. Expanding sampling to lesser-studied locations, such as Africa and the Near East has the potential to improve our understanding of the roles that microbiota play in our health. In this thesis, I obtain ancient DNA from calcified dental plaque (calculus) to describe the first oral microbiomes from ancient Near Eastern individuals over a 7000-year span. This ground-breaking data allowed me to explore the impact of agriculture at the earliest sites of agriculture in ancient Egypt and the Levant. First, I explore how research into the nascent field of microbiome has evolved over the past two decades and how microbiome research may be influenced by new interactions between the human genome and microbiome. Second, I examine the impact of widely used and novel ancient DNA extraction and library preparation methods on microbiome composition and assess methods that could allow future researchers to obtain higher yields of ancient DNA from dental calculus samples from poorly preserved samples. Third, I use ancient and historic shotgun oral metagenomes obtained from dental calculus remains of individuals from Africa, the Near East and Asia to explore the oral microbiome of ancient hunter-gatherers and agriculturalists to examine how the transition to agriculture could have impacted modern health. I also compare these individuals with those from Europe, which are better studied, to reveal the impact of environment and diet on the microbiome. While I find few significant differences between ancient hunter- gatherers and agriculturalists in the composition of species present within ancient oral microbiomes, the largest difference observed was in functions present within the two groups. This suggests that diet may drive functional differences in oral microbiomes between ancient hunter-gatherers and agriculturalists, while composition may be influenced by other factors, such as microbial ecology in the oral cavity, host genetics, oral hygiene, and environment. Finally, using saliva samples, I examine differences in the oral microbiomes of two contemporary African populations with different sustenance strategies (hunter-gatherers and farmers) living in close proximity in Central Africa and compare them to other westernised and non-westernised populations. My results show that Industrialisation results in lower oral microbial diversity and an increase in potentially oral disease-causing bacteria. This suggests non-Industrialised individuals likely had a balance between beneficial bacteria and disease-causing bacteria in their mouths, while microbiota from Industrialised individuals may be in a state of imbalance, with the presence of certain specific disease-causing bacteria shifting the overall community composition to a state of disease. These results will be of great value to our understanding of how disease, changes in human diet, and environment impact our oral microbiome, while further enriching our understanding of human prehistory.