The human gut contains microorganisms (gut microbiome) that have complex interactions with one another and their human hosts. Recent research on microbiome diversity and composition has shown that the gut microbiome (GM) has a large influence on nutrition, metabolism, and immune response. These studies have focused primarily on urban populations from industrialized countries that have increased access to health resources and diets enriched in highly-processed food. However, less is known about the GM in non-industrialized settings. The shift from hunting and gathering to agriculturalist and pastoralist practices occurred relatively recent in human history (within the last 10,000 years), and modern hunter-gatherers may possess novel GM composition. This project will study the GM of African populations who have adapted to a range of environments and foods as they spread through the continent, to understand how GMs have co-evolved with their human hosts and with human parasites. The research will expand what is known about normal human variation in GMs, and how differences in the microbiome (including in the industrialized world) may influence health. The project will support teaching and training opportunities for students, local community outreach, education and capacity building at the study sites, and international collaborations.<br/><br/>This research will assess fundamental questions about human adaptation and biology by characterizing GMs and soil-transmitted helminth (STH) and schistosomiasis (collectively referred to as helminths) parasite infections across ethnically and geographically diverse African populations with a range of subsistence practices. Fecal samples, ethnographic data, and nutrition surveys will be collected from African pastoralists, agriculturalists, and hunter-gatherers. Quantitative PCR (qPCR) will be used to test fecal DNA for several common species of helminths, including the giant roundworm Ascaris lumbricoides and fluke Schistosoma mansoni. Next-generation sequencing of 16S ribosomal bacterial and archaeal DNA (16S rDNA) and internal transcribed spacer (ITS1) region of fungal DNA will characterize GMs, and association testing will be done on GM composition and diversity with diet, subsistence, geography, presence, absence, and abundance of helminths, and genetic ancestry. The research expands knowledge of the spectrum of normal human variation in GM and the impact of helminth infection on GM composition. This project is also of broader significance for global public health since helminth infection is a major disease burden in Africa. This project can increase our biomedical understanding of the distribution of helminths and their relationships with GM composition as potentially correlated factors in the pathogenesis of disease.