THE RESPONSE to tamoxifen, a cornerstone drug in preventing breast cancer recurrence, may hinge on an unexpected factor: gut bacteria. A groundbreaking study reveals that the gut microbiome significantly influences tamoxifen pharmacokinetics, offering new insights into why nearly half of patients experience suboptimal outcomes.
Despite the well-established role of liver enzymes in activating tamoxifen, they alone cannot explain variations in drug efficacy among patients. Researchers found that gut bacteria contribute to these differences through enzymatic activity that varies between individuals. Using mouse models treated with antibiotics and donor microbiota, scientists identified β-glucuronidase (GUS) enzymes as key players in processing tamoxifen metabolites.
Interestingly, while tamoxifen did not alter the overall composition of gut bacteria, it led to distinct metabolic profiles among microbiomes. This enzymatic diversity may explain individual variations in drug response. Given that tamoxifen is administered orally, these findings underscore the gut microbiome’s role in the drug’s metabolism, paving the way for personalized treatments tailored to a patient’s microbiota.
With over 500,000 U.S. patients using tamoxifen annually, this research highlights the potential of microbiome-based strategies to enhance therapeutic efficacy, reducing recurrence and improving outcomes for the one in eight women facing breast cancer.
Reference: Alam Y et al. Variation in human gut microbiota impacts tamoxifen pharmacokinetics. mBio. 2024;0:e01679-24. [ePub ahead of print].
