Tamoxifen is the mainstay treatment for estrogen-positive breast cancer for over half a century. However, a significant proportion of patients experience disease recurrence due to treatment failure attributed to various factors, including disease pathology, genetics, and drug metabolism. Alam et al. introduce gut microbiota as a key factor influencing tamoxifen pharmacokinetics (Y. Alam, S. Hakopian, L. Ortiz de Ora, I. Tamburini, et al., mBio 16:e01679-24, 2024, https://doi.org/10.1128/mbio.01679-24). The authors present compelling evidence that functional differences in the gut microbiota, specifically the bacterial enzyme β-glucuronidase, leads to inter-individual variability in systemic exposure of tamoxifen, affecting drug efficacy. This study provides novel insights into the impact of the gut microbiota on tamoxifen pharmacokinetics, the latest example of how pharmacomicrobiomics, or the study of drug-microbe interactions, can enhance precision medicine for numerous diseases.
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