Redefining a new genomic blueprint of the human gut microbiota

The human gut microbiota composition is linked to both health and disease, but knowledge of individual microbial species is needed to decipher their biological role. Despite extensive culturing and sequencing efforts, the complete bacterial repertoire of the human gut microbiota remains undefined. Here we identify 1952 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. Whilst 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 over 200 %. These candidate species encode hundreds of novel biosynthetic gene clusters and possess a distinctive functional capacity that might explain their elusive nature. We also highlight newly identified species overrepresented in patients with gastrointestinal diseases, suggesting an underappreciated role in human health and disease. Our work uncovers the uncultured gut bacterial diversity, providing unprecedented resolution for taxonomic and functional characterization of the intestinal microbiota.