In vitro models to study Clostridioides difficile infection: current systems and future advances

Purpose of reviewClostridioides difficile infection (CDI) is the most common cause of healthcare-associated diarrhoea in western countries, being categorized as an urgent healthcare threat. Historically, researchers have relied on the use of in vivo animal models to study CDI pathogenesis; however, differences in physiology and disease prognosis compared with humans limit their suitability to model CDI. In vitro models are increasingly being used as an alternative as they offer excellent process control, and some are able to use human ex-vivo prokaryotic and/or eukaryotic cells.Recent findingsSimulating the colonic environment in vitro is particularly challenging. Bacterial fermentation models have been used to evaluate novel therapeutics, explore the re-modelling of the gut microbiota, and simulate disease progression. However, they lack the scalability to become more widespread. Models that co-culture human and bacterial cells are of particular interest, but the different conditions required by each cell type make these models challenging to run. Recent advancements in model design have allowed for longer culture times with more representative bacterial populations.As in vitro models continue to evolve, they become more physiologically relevant, offering improved simulations of CDI, and extending their applicability.

Automated summary

Historically, in vivo animal models have been used to study CDI, but their limitations in mimicking human physiology and disease prognosis have led to the increasing use of in vitro models. In vitro models offer excellent process control and the ability to use human cells, making them a valuable alternative.