A Type of Bile Acid Could Boost Cancer Immunotherapy

Salk Institute research reveals how bile acids influence liver cancer progression.

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What is in your bile acids may have an affect on liver cancer, according to a new study.

Certain bile acids, naturally produced by the body and available as dietary supplements, prevented liver cancer growth, while others encouraged tumor growth.

In an animal study, researchers studied how 20 different bile acids, which are produced in our digestive system, affect the health of T cells, a type of immune cell that helps fight off infections.

They found that adding ursodeoxycholic acid (UDCA) significantly reduced tumor growth in mice with liver cancer. UDCA is typically used to dissolve gallstones and improve liver function in people with certain liver diseases.

“Considering how T cell performance varies across different organs, tissues, and tumors puts us at a great vantage point for looking at ways to optimize cancer treatment,” Siva Karthik Varanasi, a former postdoctoral researcher at Salk, said in a press release. “By taking this unique approach, we’re able to see that bile acids in the liver are hugely influencing T cells’ ability to do their job and therefore may be a useful therapeutic target.”

Managing Tumor Growth

Through analyzing liver cancer tissue, researchers found increased levels of certain bile acids. When they blocked the production of these bile acids in mice, the tumors shrank. This suggests that controlling bile acid production could improve how well cancer immunotherapy works.

Blocking one protein involved in making bile acids, combined with adding UDCA, controlled tumor growth in mice with liver cancer.

“Livers have a particularly unique environment, but we didn’t really understand how it was affecting the immune and cancer cells,” Susan Kaech, who has a doctorate in developmental biology and is the senior author of the study, said in a statement.

UDCA enhanced the activity of cancer-fighting cells, suggesting that increased levels of this bile acid, achievable through dietary supplementation, could improve cancer treatment efficacy.

“We’re already a huge step ahead when it comes to translating our findings to the clinic, because UDCA supplementation is already used to treat liver disease and could easily be tested in liver cancer next,” Kaech stated. UDCA is currently used to treat a condition called primary biliary cholangitis (PBC), a chronic autoimmune disease that damages bile ducts in the liver; it increases our risk for liver cancer, leads to liver scarring, and eventually liver failure.

The liver produces over 100 different bile acids that assist in digestion, but excessive bile acids are linked to poor health and cancer progression. Previous studies did not isolate the effects of individual bile acids, leaving their specific roles in cancer unclear.

Another type of bile acid, lithocholic acid (LCA), which is present in lower concentrations than many other bile acids and is important for fat digestion and absorption, was found to weaken T cell function, meaning it made T cells less effective.

It’s not surprising to see a study that demonstrates that bile acids contribute to the difficulty in treating liver cancers, Dr. Mary E. Edgerton, professor of pathology at the University of Nebraska Medical Center, told The Epoch Times.

“Statins, widely used for control of the body’s synthesis of cholesterol, a key component of bile acids, reduce the risk for liver cancer,” she said. “Perhaps this is because they decrease the synthesis of cholesterol, a key component of bile acids.”

Dietary and Microbiome Interventions

Dietary and microbiome interventions are emerging areas of research in liver cancer treatment, focusing on the intricate relationship between the gut microbiome and liver health.

Since the secondary bile acids made by the gut microbiome have a stronger effect on the immune system than primary ones made by the liver, this approach has the potential to improve response to immunotherapy, Edgerton said.

“In fact, there has been a great deal of research showing that differences in content of the gut microbiome affect the efficacy of immunotherapy in melanoma,” she added. “Could it be that this is accomplished by changing the distribution of bile acids to favor UCDA?”

Research indicates that dietary interventions affecting the gut microbiome can significantly impact liver health, especially in the prevention and treatment of liver cancer.

The composition of the gut microbiome in patients with liver cancer differs from that of healthy people, with specific bacterial species and their metabolites affecting the tumor environment and immune responses.

Evidence-based dietary and microbiome interventions include:

Diet

Dietary interventions, such as adopting a Mediterranean-style diet, increasing fiber intake, or incorporating specific fatty acids (like omega-3s), may improve liver health and potentially modify gut microbiome composition, potentially enhancing cancer treatment outcomes.

Probiotics and Prebiotics

Probiotics (live microorganisms) and prebiotics (food ingredients that promote the growth of beneficial bacteria) can help modulate the gut microbiome, potentially improving liver function and influencing the tumor microenvironment.