A new genomic blueprint of the human gut microbiota

The composition of the human gut microbiota is linked to health and disease, but knowledge of individual microbial species is needed to decipher their biological roles. Despite extensive culturing and sequencing efforts, the complete bacterial repertoire of the human gut microbiota remains undefined. Here we identify 1,952 uncultured candidate bacterial species by reconstructing 92,143 metagenome-assembled genomes from 11,850 human gut microbiomes. These uncultured genomes substantially expand the known species repertoire of the collective human gut microbiota, with a 281% increase in phylogenetic diversity. Although the newly identified species are less prevalent in well-studied populations compared to reference isolate genomes, they improve classification of understudied African and South American samples by more than 200%. These candidate species encode hundreds of newly identified biosynthetic gene clusters and possess a distinctive functional capacity that might explain their elusive nature. Our work expands the known diversity of uncultured gut bacteria, which provides unprecedented resolution for taxonomic and functional characterization of the intestinal microbiota.