ACaenorhabditis elegansbased system for high-throughput functional phenotyping of human gut microbiota

Summary Bottoms-up approach of mono or poly colonizing microbes in germfree model is an important tool for mechanistic understanding of human gut microbiota. However, doing this in models such as germfree mouse is expensive and time consuming. To address this problem, we developed a Caenorhabditis elegans based screening system. We used a gut microbiota culture collection that represents more than 70% functional capacity of the human gut microbiome to anaerobically colonize C. elegans . We chose colonization resistance as the phenotype of the microbiome for further screening and found that half of the strains, previously identified in vitro as inhibiting Clostridioides difficile , also did so in C. elegans . When validated using germ-free mouse model, results were in concordance with that obtained from C. elegans model. Our system therefore could be used for screening large number of bacterial species to better understand host-microbiome interaction.