Global-scale microbiome analyses identify an ancestral gut cyanobacterial lineage enriched in African populations

Abstract Industrialization has profoundly reshaped the structure and function of the human gut microbiome, yet our current knowledge of its diversity remains heavily biased toward industrialized populations. Here, we performed an integrated analysis of a large-scale metagenomic dataset (n = 41,471) to systematically characterize the gut microbiome across the African continent. We show that sub-Saharan African populations harbor gut microbiome structures that are distinct not only from industrialized populations but also from other non-industrialized populations. Notably, we identify a strong enrichment of Gastranaerophilales, a poorly characterized lineage of non-photosynthetic Cyanobacteria, in sub-Saharan African populations. Comparative genomic analyses reveal that this lineage encodes distinctive functional features, including motility-related genes, vitamin biosynthesis pathways, and specialized carbohydrate transport systems. Furthermore, we show that this lineage is widely distributed across non-human primates, supporting an evolutionarily conserved host association predating modern humans. Together, our findings identify Gastranaerophilales as a potential ancestral gut symbiont that has been markedly reduced in industrialized societies but retained within African populations, highlighting a major but previously underappreciated component of the human gut microbiome. Competing Interest Statement The authors have declared no competing interest.