We demonstrate an easy to set up model of the human large intestine incorporating four colonocyte/enterocyte cell lines, tight and loosely bound mucosal layers, and faecal inoculum from a healthy volunteer. We have successfully shown how the model can capture the dynamic crosstalk between colonocytes and commensal bacteria on a molecular level with spatial resolution. We have demonstrated the ability of the model to detect changes in the metabolic profile of commensals as a function of exogenous species such as APIs. Furthermore, our model benefits from being easy to set up and analyse using short (< 10 minute) CSI experiments, potentially aiding the development and screening of future targeted colonic drug delivery systems and APIs using live bacteria and colonocytes. The set-up can be inoculated with an individual's stool and harvested colonocytes, potentially enabling the development of personalised medicine for colorectal pathologies.