Michael Zimmermann, Matthias Ebert and Tianzuo Zhan

Our research interest

Anti-cancer drugs often show pronounced interpersonal variation in drug response, as well as dose- and treatment-limiting adverse effects. Accumulating evidence suggests that the intestinal microbiome and its capacity to metabolize drugs play an important role for these interpersonal differences. Therefore, the gut microbiota could serve as a biomarker and target to optimize cancer therapy and alleviate adverse effects.

Our research collaboration combines expertise in clinical and translational oncology (Ebert, Zhan) with cutting-edge technologies for experimental microbiome studies (Zimmermann) to unravel the contribution of the gut microbiome to clinical responses to anti-cancer therapy.

Background

The human gut microbiota plays a vital role in human health and disease, by catabolizing food components and contributing to host metabolism. Recently, the gut microbiota was shown to actively metabolize therapeutic drugs, thereby affecting their availability and efficiency. Interpersonal variations in drug response and adverse-effects are a major challenge to personalized oncology. Currently, only few biomarkers are available that can predict therapy outcome for the majority of anti-neoplastic drug. The contribution of the gut microbiota to metabolism of anti-cancer drugs and their subsequent effects on therapy response in humans are poorly understood. 

Goals

Our interdisciplinary collaboration will establish a novel pipeline to systematically quantify the impact of gut microbial metabolism of anti-cancer compounds on drug response and adverse effects. This will pave the ground to establish microbiome-encoded predictors of therapy response and toxicity, and uncover functional links between gut drug metabolism and tumor biology that may be therapeutically exploited.

Our current and future goals are:

• to systematically characterize the capacity of gut microbes to metabolize anti-cancer drugs of clinical relevance
• link microbiota drug metabolism to the efficiency and adverse effects of anti-cancer drug therapies in patients
• mechanistically connect microbiota drug interactions to specific tumor phenotypes at the molecular level using a combination of microbiota and organoid culturing approaches.