<italic>In vitro</italic> cellular model systems provide a promising alternative to animal experiments for studying the intestine-organ axis.

AbstractLimiting animal experiments is essential for ethical issues and also because scientific evidence highlights the discrepancies between human and animal metabolism. This review aims to provide a critical discussion of the strengths and limitations of the most appropriate <italic>in vitro</italic> intestine model to answer complex research questions in pharmaceutical and nutraceutical fields. This review describes the components contributing to the definition of the gut barrier structure, from the outer mucus layer to the inner part of lamina propria, including endothelial and neuronal networks. We conclude that the main advantage of these co-culture models is their versatility since they are modulable systems in which each component can be added, changed, or removed to reproduce a specific physiological condition each time. Additionally, we compare intestinal organoid models and microfluidic systems with well-established co-culture models. [ABSTRACT FROM AUTHOR]