Tamoxifen is a widely used treatment aimed at preventing the recurrence of breast cancer. Recent research indicates that variations in an individual’s gut microbiome may influence the drug’s effectiveness.
A recent study reveals that differences in a person’s gut microbiota can affect the pharmacokinetics of tamoxifen, impacting how well the medication works. This research, published in the journal mBio by the American Society for Microbiology, implies that in the future, healthcare providers may be able to use simple stool tests to identify specific gut bacteria that could help predict a patient’s response to tamoxifen.
“The main takeaway from this study is that while tamoxifen is a key treatment to prevent breast cancer from coming back, almost 50% of patients don’t have a good response to it,” explained lead author Yasmine Alam, a Ph.D. candidate in the Department of Biological Chemistry at the University of California, Irvine. “As tamoxifen is taken orally and processed by the gut, the variations in patient responses might be connected to the gut microbiome—the vast array of bacteria residing in our intestines that differ significantly from person to person. Our research seeks to deepen the understanding of how these gut bacteria influence tamoxifen’s absorption, breakdown, and recycling in the body to enhance treatment outcomes for those battling breast cancer.”
In this study, the researchers aimed to determine the role of gut microbes in processing tamoxifen (including its absorption, distribution, metabolism, and excretion), especially given its diverse effectiveness among different patients. They administered tamoxifen to mice without a gut microbiome and to others that had received a human microbiome from a fecal sample. The results indicated that mice with their gut bacteria displayed higher levels of tamoxifen in their blood. The scientists subsequently sought to identify which components of the gut microbiome influenced the drug’s blood concentration, ultimately connecting a specific bacterial enzyme, beta-glucuronidase, to the drug’s entry into the bloodstream.
When a person ingests a tamoxifen pill, it travels through the stomach and into the intestines, where it is absorbed into the bloodstream. Once in the bloodstream, tamoxifen goes to the liver, where it is converted into a more potent form to combat breast cancer. However, a sugar molecule can occasionally attach to the drug, prompting the body to remove the cancer-fighting version back into the intestine instead of allowing it to enter the bloodstream for distribution to areas needing treatment. This transformation must occur by removing the sugar molecule—researchers found that the enzyme beta-glucuronidase produced by gut bacteria helps detach the sugar from tamoxifen, enabling it to combat breast cancer effectively.
“We specifically identified that certain enzymes from gut bacteria, known as β-glucuronidase, are involved in the breakdown of tamoxifen. These enzymes assist in recycling tamoxifen back into the bloodstream, enhancing the drug’s efficacy,” said Alam. “Our findings show a strong connection between a particular bacterium, Bacteroides fragilis, and the positive impact of these enzymes on tamoxifen blood levels. This indicates that the gut microbiome plays a crucial role in the effectiveness of tamoxifen treatment.”
The ultimate aim of this research is to facilitate the development of more personalized and effective treatment strategies to prevent the recurrence of breast cancer.
The research was spearheaded by Elizabeth Bess, Ph.D., an assistant professor in the department of chemistry at UC Irvine, and Cholsoon Jang, Ph.D., an assistant professor in the department of biological chemistry at UC Irvine.
