Cultivation-based multiplex phenotyping of human gut microbiota allows targeted recovery of previously uncultured bacteria

The human gut microbiota is linked to a variety of human health issues and implicated in antibiotic resistance gene dissemination. Most of these associations rely on culture-independent methods, since it is commonly believed that gut microbiota cannot be easily or sufficiently cultured. Here, we show that carefully designed conditions enable cultivation of a representative proportion of human gut bacteria, enabling rapid multiplex phenotypic profiling. We use this approach to determine the phylogenetic distribution of antibiotic tolerance phenotypes for 16 antibiotics in the human gut microbiota. Based on the phenotypic mapping, we tailor antibiotic combinations to specifically select for previously uncultivated bacteria. Utilizing this method we cultivate and sequence the genomes of four isolates, one of which apparently belongs to the genus Oscillibacter; uncultivated Oscillibacter strains have been previously found to be anti-correlated with Crohn's disease.