Document Type

Article

Publication Date

2025

DOI

10.1128/jb.00407-24

Publication Title

Journal of Bacteriology

Volume

Article in Press

Pages

17 pp.

Abstract

Clostridioides difficile infection (CDI) is an urgent public health threat with a high rate of recurrence and limited treatment options. In vivo models have been indispensable in understanding CDI pathophysiology and establishing treatment protocols and continue to be essential in pre-clinal testing. More importantly, in vivo models offer the opportunity to probe the complex systemic host response to the microbe, which is impossible to recapitulate in vitro. Nonetheless, constraints related to the availability of animal models, cost, ethical considerations, and regulatory control limit their accessibility for basic research. Furthermore, physiological and habitual divergences between animal models and humans often result in poor translatability to human patients. In addition to being more accessible, in vitro CDI models offer more control over experimental parameters and allow dynamic analysis of early infection. In vitro fermentation offers models for probing microbe-microbe and microbe-microbiome interactions, while continuous multi-stage platforms allow opportunities to study C. difficile pathophysiology and treatment in context with human-derived microbiota. However, these platforms are not suitable for probing the host-pathogen interface, leaving the challenge of modeling early CDI unanswered. As a result, alternative in vitro co-culture platforms are being developed. This review evaluates the strengths and weaknesses of each approach, as well as future directions for C. difficile research.

Rights

© 2025 Zvonareva et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License.

Original Publication Citation

Zvonareva, T., Courson, D. S., & Purcell, E. B. (2025). Clostridioides difficile infection study models and prospectives for probing the microbe-host interface. Journal of Bacteriology. Advance online publication. https://doi.org/10.1128/jb.00407-24

ORCID

0009-0001-3865-1760 (Zvonareva), 0000-0002-8736-0433 (Purcell)

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