Investigating the impact of flow on tight junctions in a novel model of the gut barrier

Abstract: Physiologically relevant and predictive models of the gut barrier are vital for investigating all areas of gut health and disease, from the gut microbiota to bowel cancer. The majority of gut studies currently rely on animal models or static cell cultures which both have inherent disadvantages with regards to expense, time and translatability. In the present study, a novel model produced by Kirkstall Ltd is studied, which introduces fluid flow as a factor into cell culture models of the gut epithelia. Flow is known to affect other tissues where fluid flow is high for example circulatory endothelia and cells lining the urinary tract, however the effect of flow on gut cells has been studied very little.

Particularly, we focus on the impact of flow on tight junctions. Tight junctions allow epithelial monolayers to form tight barriers, preventing passage of cells, molecules and microorganisms paracellularly. They also allow selective permeability to nutrients and electrolytes depending on their expression and localisation within a tissue. These are vital functions particularly within the gut epithelia, where gut lumen contents must be kept separate from the rest of the body but some reabsorption of nutrients is required.

Using several different colonocyte cell lines, we investigate the impact of physiological fluid flow on the gene and protein level expression of tight junctions compared to traditional static cell culture techniques. By characterising this novel model, we hope to provide a tool with greater translatability and relevance for future research into gut health and disease.