Population studies provide insights into the interplay between the gut microbiome and geographical, lifestyle, genetic and environmental factors. However, low- and middle-income countries, in which approximately 84% of the world’s population lives
1, are not equitably represented in large-scale gut microbiome research
2,3,4. Here we present the AWI-Gen 2 Microbiome Project, a cross-sectional gut microbiome study sampling 1,801 women from Burkina Faso, Ghana, Kenya and South Africa. By engaging with communities that range from rural and horticultural to post-industrial and urban informal settlements, we capture a far greater breadth of the world’s population diversity. Using shotgun metagenomic sequencing, we identify taxa with geographic and lifestyle associations, including
Treponema and
Cryptobacteroides species loss and
Bifidobacterium species gain in urban populations. We uncover 1,005 bacterial metagenome-assembled genomes, and we identify antibiotic susceptibility as a factor that might drive
Treponema succinifaciens absence in urban populations. Finally, we find an HIV infection signature defined by several taxa not previously associated with HIV, including
Dysosmobacter welbionis and
Enterocloster sp. This study represents the largest population-representative survey of gut metagenomes of African individuals so far, and paired with extensive clinical biomarkers and demographic data, provides extensive opportunity for microbiome-related discovery.