Speaker
Description
The gut microbiota plays a vital role in maintaining human health by contributing to nutrient metabolism, immune function, and the production of bioactive metabolites, and is implicated in inflammatory, metabolic, and neurological disorders, underscoring its important influence on human physiology. Beyond these roles, the gut microbiota is increasingly recognized as an important factor influencing drug biotransformation and contributes to interindividual variability in drug response.
Cytochrome P450 (CYP) enzymes are major contributors to human drug metabolism, mediating the oxidative biotransformation of a broad spectrum of xenobiotics and therapeutic agents. Because CYP activity influences drug efficacy and safety, alterations in their function may have important pharmacological consequences. To investigate the effects of the microbial metabolite Urolithin A (UroA) on CYP activity, we performed inhibition assays using human liver microsomes.
Our findings show that UroA significantly inhibited CYP1A1/2 activity (IC50 =6.2μM) and CYP3A4 activity (IC50 =7.6μM) when testosterone was used as the marker substrate. In contrast, no inhibition of CYP3A4 activity was observed with midazolam, indicating substrate-dependent inhibition and selective active-site interactions. In addition, CYP mRNA expression in primary human hepatocytes was quantified to assess possible transcriptional modulation by UroA, providing further insight into the molecular basis of UroA–CYP interactions. As strategies to enhance human health increasingly focus on targeting the gut microbiota or supplementing microbial metabolites such as UroA, it is essential to understand their potential impact on drug metabolism and pharmacotherapeutic outcomes.
Supported by The Czech Science Foundation grant No.23-05645S and by Grant Agency of Palacký University IGA_LF_2026_028.
