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

Abstract

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.

MiGut: A scalable in vitro platform for simulating the human gut microbiome—Development, validation and simulation of antibiotic‐induced dysbiosis

“…In general, in vitro models (including MiGut) offer a very useful tool for simulating the GM. However, a criticism of these systems is that they can be over‐simplistic and fail to adequately simulate some of the complexity of the in vivo environment (Ewin et al, 2023 ). For example, it has been shown that there are differences between the sessile and planktonic bacterial communities of the colon, and the ability to sample both groups would give a more complete view of the GM (Bircher et al, 2020 ; Crowther et al, 2016 ).…”