Clostridioides difficile infection study models and prospectives for probing the microbe-host interface
Tatiana Zvonareva1, David S Courson1, Erin B Purcell1
1Department of Chemistry & Biochemistry, Old Dominion University, Norfolk, Virginia, USA.
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.
Insights
Clostridioides difficile infection (CDI) research faces challenges with current animal models. This review explores alternative in vitro models for better understanding CDI and developing new treatments.
Area of Science:
- Microbiology
- Infectious Diseases
- Translational Research
Background:
- Clostridioides difficile infection (CDI) is a significant public health concern with high recurrence rates and limited therapeutic options.
- In vivo models are crucial for studying CDI pathophysiology and preclinical testing but face limitations in accessibility, cost, ethics, and translatability.
- Existing in vitro models offer control and dynamic analysis but struggle to fully capture the host-pathogen interaction essential for early CDI stages.
Purpose of the Study:
- To review and evaluate the strengths and weaknesses of various in vivo and in vitro models for Clostridioides difficile infection research.
- To identify current limitations in modeling CDI, particularly the host-pathogen interface.
- To discuss future directions and alternative approaches for improved CDI research models.
Main Methods:
- Literature review of existing in vivo and in vitro models for Clostridioides difficile infection.
- Comparative analysis of the advantages and disadvantages of each modeling approach.
- Discussion of emerging in vitro co-culture platforms.
Main Results:
- In vivo models provide insights into systemic host response but have translatability issues.
- In vitro fermentation and continuous platforms allow study of microbe-microbe and microbe-microbiome interactions.
- Current in vitro models are insufficient for studying the host-pathogen interface in early CDI.
Conclusions:
- A critical evaluation of current CDI models is necessary to address research gaps.
- Development of advanced in vitro co-culture systems is crucial for modeling the host-pathogen interface.
- Future research should focus on creating more accessible, translatable, and comprehensive models for CDI.
