Abstract Background Crohn’s disease (CD) is a chronic, relapsing–remitting gastrointestinal inflammatory condition with a multifactorial etiology. At present, drug therapy is the most important treatment option. However, a substantial number of CD patients experience side effects and/or nonresponse to medical drugs. In part, this might be attributed to the interaction of the intestinal microbiome with xenobiotics, such as medical drugs. The aim of this study was to explore the effect of the common CD drugs budesonide, 6-mercaptopurine (6-MP), as well as tofacitinib on the CD patient’s microbiome in vitro. Results We performed 16S rRNA gene-based bacterial community profiling and metaproteomic analyses on anaerobic ex vivo incubations of CD patient-derived fecal microbiota (FM) that were exposed to CD drugs or control conditions. Both bacterial community profiling and metaproteomics revealed larger differences in 24-h FM incubations between the five donor-derived FM samples than between the various drug incubations. Incubation of the FM of one of the donors with 6-MP or tofacitinib resulted in a significant alteration in the metaproteome when compared to the control condition, whereas no effect could be observed upon incubation with budesonide. Considering only bacterial proteins detected in at least 80% of either the drug or control FM incubations, 33 proteins were consistently more abundant and 93 less abundant in all five donor-derived samples with 6-MP incubation, distinguishing 6-MP from control conditions. In contrast to metaproteomic analyses, bacterial community profiling only detected a significantly lower relative abundance of Colidextribacter in 15 µg/ml tofacitinib FM incubations. No alterations were detected in overall bacterial richness, diversity, or community structure in response to incubation with any of the drugs. Conclusions Tofacitinib and especially 6-MP significantly affect microbial function, but barely microbial composition in vitro. These drug-induced functional changes may subsequently influence host physiology and potentially inflammation in CD. Our findings emphasize the relevance to include functional microbial studies when investigating drug–microbiota interactions. Further research is needed to elucidate the impact of 6-MP-induced microbial alterations on intestinal physiology and inflammation in CD.
Becker et al. (Sat,) studied this question.