Introduction. A substantial number of Crohn’s disease (CD) patients experience side-effects and/or non-response to medical drugs. In part, this might be attributed to the interaction of the intestinal microbiome with xenobiotics. The aim of this study was to explore the effect of common CD drugs on the patient’s microbiome in vitro. Methods The fecal microbiome of each of 5 CD patients was exposed to 42 μg/ml budesonide, 55 μg/ml 6-mercaptopurine (6-MP), 5 or 15 μg/ml tofacitinib, or DMSO-control in defined culture medium in an anaerobic chamber at 37°C for 24 hours. Subsequently, DNA and proteins were isolated and subjected to 16 rRNA gene amplicon sequencing and LC-MS proteomic analysis, respectively.