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Caenorhabditis elegans model for in vivo screening of human gut microbiota mediated colonization and colonization resistance against Clostridioides difficile

2024/02/27 by Achuthan Ambat, Vishnu Thayyil Valappil, Sudeep Ghimire +7 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Clostridium difficile and Clostridium perfringens research #Genetics, Aging, and Longevity in Model Organisms #Gut microbiota and health

paper · pdf · doi:10.1101/2024.02.27.582212

openalex publication_date 2024/02/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28

Abstract

Abstract The conventional bottom-up approach to probing the human gut microbiome’s 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 microbiome’s 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 microbiome’s 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 model’s translational potential.

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