Nonmammalian models to study Clostridioides difficile infection; a systematic review

Clostridioide difficile is the leading cause of diarrhea disease worldwide and is a CDC-designated urgent threat level pathogen. Mammalian models are commonly utilized as gold standard to study the patho-genesis of C. difficile infection (CDI); however, alternatives are needed due to cost, higher throughput ability, and mammalian animal ethics. Nonmammalian models such as great wax worm, nematode, fruit fly, and zebrafish have been used as CDI models. This review provides a comprehensive summary of nonmammalian models used to study CDI. Multiple studies were identified using these models to study C. difficile infection, pathogenicity, colonization, host immunity, and therapy. Translational outcomes and strength and weakness of each nonmammalian model are discussed.(c) 2023 Elsevier Ltd. All rights reserved.

Automated summary

Clostridioide difficile is the leading cause of diarrhea disease worldwide and is considered an urgent threat pathogen by CDC. Mammalian models are commonly used to study C. difficile infection, but alternative nonmammalian models, such as great wax worm, nematode, fruit fly, and zebrafish, have been explored due to cost, throughput capacity, and ethical concerns. This review provides a comprehensive summary of the use of nonmammalian models in studying CDI, including its infection mechanism, pathogenicity, colonization, host immunity, and therapy. The translational outcomes and strengths and weaknesses of each nonmammalian model are discussed.