The human gut is remarkably diverse, encompassing more than 4,500 identified microbial species. However, ~70% of these species lack cultured representatives, limiting our functional understanding to predictions based on bioinformatic analyses. Here, we developed an innovative platform for the high-throughput cultivation of microorganisms designed to bring the uncultured majority of the human gut microbiome into culture for the first time.
The novel platform uses fluorescence-activated cell sorting modified for microoxic sort conditions, for the high-throughput isolation and axenic culture of microorganisms from human fecal samples. Cultured isolates were genome sequenced for taxonomic identification and genomic analyses, and cryopreserved in a dedicated biobank.
Using this approach, we have generated a biobank of >12,000 isolates from 50 human fecal samples. The sequenced isolates span both prokaryote domains, including 11 phyla, 12 classes, 28 orders, 53 families, 207 genera, and at least 525 distinct species. Of these, 51% of species, 21% of genera, 15% of families and 7% of orders represent previously uncultured lineages, including multiple genera and species identified for the first time. Importantly, we have also recovered the first representatives of many key gut lineages, including order UBA1381, family CAG-272, and family CAG-74.
With ongoing exponential increases to our culturing efforts, we predict our platform will provide cultured representatives for >50% of the human gut microbiome. Characterisation of these novel isolates will substantially improve our understanding of the human microbiome and provide an invaluable resource for future research.