Files
Abstract
This dissertation consists of two projects using microbial genomic data to investigate the relationship between humans and their diets. The first project presents the South Asian MicroBiome ARray (SAMBAR), a population-scale 16S gut microbiome study of 575 adults from ten geographically and socio-culturally diverse South Asian communities. Each community was sampled in ancestral villages and urban centers, enabling controlled comparisons of geography and lifestyle. Relative to global cohorts, SAMBAR microbiomes occupy a distinct compositional space with stronger correlation to geography and community membership than lifestyle. Although urbanization is consistently associated with increased abundance of disease-linked taxa, microbiome responses to lifestyle transitions are largely community-driven, including the acquisition of wheat- and dairying-associated microbial modules in some communities that may facilitate non-genetic adaptation to lactase non-persistence. Microbiome responses to urbanization are heterogeneous even at regional scales, reflecting local culture and geography and underscoring the need for community-specific investigations of health impacts. The second project uses ancient metagenomic methods to investigate Streptococcus mutans, a key cariogenic bacterium that metabolizes dietary carbohydrates into enamel-eroding acid. We analyze ancient oral microbiomes from 51 human tooth samples recovered from the El Olivar archaeological site in Chile, ranging from 1157 to 1538 CE. Taxonomic classification reveals predominantly soil-associated microbial communities, as expected for archaeological remains, but also identify endogenous oral taxa in a subset of samples, including taxa previously associated with ancient oral microbiomes. We authenticate ancient S. mutans DNA in 12 samples, and select eight samples for targeted capture and enrichment of phylogenetically informative and virulence-associated S. mutans genes. Phylogenetic analysis integrating ancient and modern strains reveals limited geographic structure, consistent with the high transmissibility of S. mutans, and places all El Olivar samples in a distinct clade with a geographically diverse sister group. Screening for mutacin genes reveals that all eight El Olivar individuals harbor at least one mutacin, and analysis of an 84-bp dextranase gene fragment places El Olivar sequences in close phylogenetic proximity to other pre-colonial American strains. These results add temporal and spatial resolution to our understanding of S. mutans’s virulence and evolution. Together, these projects highlight the potential of microbial genomics to study human diets and lifestyles on both short and long term timelines.