Scientists at Weill Cornell Medicine have uncovered a surprising new role for gut bacteria: producing bile acids that can block sex hormone signaling and help the immune system attack cancer.
In a study published April 15 in Cell, researchers found that certain bile acids, transformed by microbes in the human gut, can inhibit the androgen receptor—a key player in both development and cancer biology. When tested in mice with bladder cancer, these microbiota-modified bile acids triggered a strong antitumor immune response.
“I was very surprised by our findings,” said Chun-Jun Guo, co-senior author and associate professor of immunology in medicine. “As far as I know, no one has previously discovered molecules like these bile acids that can interact with the androgen receptor in this way.”
Primary bile acids are produced by the liver and released into the gut, where bacteria modify their structure. Guo’s team identified more than 50 new bile acid molecules previously unknown to science. Among these, several were found to directly block the androgen receptor, a molecule known to suppress immune cell activity in tumors.
“We discovered more than 50 different bile acid molecules modified by the microbiota – many of which had never been identified before,” Guo said.
In mice, the compounds enhanced the cancer-killing capabilities of CD8 T cells, a crucial immune cell type, and helped reduce tumor size. “Our results suggest that these altered bile acids help shrink tumors by enhancing T cells’ ability to survive within the tumor and destroy cancer cells,” said co-senior author Nicholas Collins.
The findings suggest potential for a new class of cancer treatments based on manipulating gut microbes or delivering specific bile acids directly. Future strategies could involve introducing targeted bacteria to patients or combining microbial bile acids with existing immunotherapies.
“This study highlights the profound and evolving partnership between the human host and its gut microbiota,” said co-senior author David Artis. “It also exemplifies the power of multidisciplinary collaboration in driving microbiome science.”
While the discovery is still in early stages, the team is now exploring how diet, microbial genetics, and other factors influence bile acid production. They hope to eventually harness these compounds to develop safer, more effective cancer therapies.
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