Rubel, Meagan
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Publication Effects Of Diet And Parasites On The Gut Microbiota Of Diverse Sub-Saharan Africans(2019-01-01) Rubel, MeaganABSTRACT EFFECTS OF DIET AND PARASITES ON THE GUT MICROBIOTA OF DIVERSE SUB-SAHARAN AFRICANS Meagan A. Rubel Sarah A. Tishkoff Contemporary African populations possess myriad genetic and phenotypic adaptations to diverse diets, varying climates, and infectious diseases. Most microbiome studies to date have focused on primarily European and Asian populations in urban, industrialized settings. By comparison, relatively little is known about traditional African gut microbiomes, and the range of variation they contain. Many African populations are undergoing substantial changes because of rapid globalization, easier access to hygienic resources and medications, shifts away from traditional lifestyle, and increased exposure to processed diets high in sugars and fats. By characterizing microbiome variation among sub-Saharan African populations using metagenomic sequencing, we can better understand differential response to diseases and environmental factors in producing physiological adaptations. Furthermore, by extending microbiome sampling across a range of traditional African populations in multiple countries, it may be possible to trace subsistence transition with changes in settlement and diet, and interrogate how these are shaped by industrialization. In this dissertation, I describe the gut microbiomes of populations practicing agropastoralism, hunting and gathering, and pastoralism in three African countries: Botswana, Cameroon, and Tanzania. To do this, I used amplicon and shotgun sequencing to characterize microbial genomes and annotate their functions. I combined this microbial data with extensive phenotype and ethnographic data. With this dataset, I detected gut microbial taxa associated with subsistence strategy, sex, geography, and host genetics. I demonstrated that the degree of industrialization in these populations correlated with enrichment of functional pathways involved in the metabolism of xenobiotics and industrial pollutants. Moreover, I found that the gut microbiome has no association with HIV infection, but is highly predictive of multiple gastroenteric parasite infections within Cameroonians. Parasite infection and microbiome composition were, in turn, associated with Th-2 proinflammatory cytokines that are produced during helminthiasis. My research captures microbiota and taxa that are rare or absent from microbiomes of industrialized populations and expands the definition of normal variation within the human gut microbiome. My dissertation identifies multiple factors affecting microbiome composition and works towards generating a more holistic interpretation of the structure and function of human gut microbiota, and their potential associations with human physiology and adaptation.