A buildup of bile acids caused by an unhealthy gut can drive breast cancer to other parts of the body, new University of Virginia Comprehensive Cancer Center research reveals, according to a July 15 announcement. The findings could open the door to new ways to prevent breast cancer metastasis, improve patient outcomes and save lives.
The research from Melanie Rutkowski, PhD, and colleagues helps explain how the gut microbiome plays a role in the spread of hormone receptor-positive (HR+) breast cancer. "We found that an unhealthy gut microbiome loses the ability to regulate the composition of bile acids, potent signaling molecules that when not properly regulated can cause havoc on your health, metabolism and the immune system. This creates an environment throughout the body that favors breast tumor metastasis," Rutkowski said. "Our findings suggest that we could reduce breast cancer metastasis either by replenishing the bacteria that can modify the composition of bile acids, or by treating breast cancer patients with bile acid sequestrants, drugs that are already FDA-approved for treating metabolic diseases."
HR+ breast cancer is by far the most common form of metastatic breast cancer in American women. It tends to spread early, with tumors often forming in lymph nodes and lungs. Once it has spread, treatment becomes more difficult and mortality risk increases.
Prior studies had linked gut microbiome imbalance with poor patient outcomes, but Rutkowski's research identifies a specific mechanism responsible for this process. The study found that gut dysbiosis led to a buildup of bile acids, which then triggered harmful inflammation fueling further spread of cancer cells, especially to lungs. Audrey Putelo, PhD and co-author, said, "We found that certain bile acids produced when the gut microbiome is disrupted can create conditions that make it easier for breast cancer cells to spread." She added, "Because bile acids can be measured and modified, this finding opens exciting possibilities for developing new approaches to identify high-risk patients and reduce likelihood of metastatic disease."
The scientists conducted their work primarily in lab mice but also examined human HR+ breast cancer patients, where they observed elevated bile acids and insulin resistance were associated with reduced survival; those who received medications suppressing bile acid tended toward longer life spans, though researchers caution more studies are needed before confirming direct benefits.
Rutkowski said, "Because many of the patients who were on bile-acid sequestrants have health issues that tend to favor a worse prognosis for breast cancer, the survival of patients who were prescribed bile-acid sequestrants and who had metastatic breast cancer are extremely encouraging." She continued, "Now we want to know if these existing FDA-approved drugs can prevent the cancer from spreading in first place...this could support use of well-tolerated class drugs for prevention." The UVA Comprehensive Cancer Center is one among 57 centers nationally designated as comprehensive by National Cancer Institute.
