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bioRxiv · 10.1101/2024.02.27.582212

A Caenorhabditis elegans based system for high-throughput functional phenotyping of human gut microbiota

Ambat, A.·Thayyil Valappil, V.·Ghimire, S.·Harnvoravongchai, P.·Mishra, S.·Vijayan Pillai, V.·Kashyap, P.·Scaria, J.
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Abstract

The conventional bottom-up approach to probing the human gut microbiomes link with hosts in germ-free models is hampered by considerable costs and time. To address this, our study introduces the nematode Caenorhabditis elegans as an innovative high-throughput model for exploring the gut microbiomes impact on functional phenotypes. Traditionally, C. elegans studies have used continuous feeding for bacterial administration, a method that is unsuitable for anaerobes. For the first time, we have standardized a protocol for colonizing C. elegans with human gut anaerobes. By screening a microbial culturomics library representing 70% of the gut microbiomes functional capacity, we showed successful colonization for 46% of the library. Functional phenotyping revealed that 5 of 10 strains, previously identified in vitro as inhibiting C. difficile, also inhibited in vivo. Validation of a selected strain in a germ-free mouse model confirmed colonization resistance and an immune response consistent with findings in C. elegans, underscoring the models translational potential.

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Ambat, A., Thayyil Valappil, V., Ghimire, S., Harnvoravongchai, P., Mishra, S., Vijayan Pillai, V., Kashyap, P., Scaria, J.. 2024-02-27. A Caenorhabditis elegans based system for high-throughput functional phenotyping of human gut microbiota. https://doi.org/10.1101/2024.02.27.582212

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