Wen Jiang, M.D., Ph.D.
Image source: University of Texas MD Anderson Cancer Center
“For decades, scientists have tried to address how aggressively the liver filters out nanomedicine by redesigning the drugs themselves. Our research shows that the host’s biology, specifically the gut microbiome, is just as important as the particle design,” Jiang said. “This is the first study to demonstrate that the gut microbiome can directly impact chemotherapy, opening up an entirely new strategy for boosting cancer treatment.”
Nanoparticle-based chemotherapy – drugs packaged inside microscopic carriers like liposomes or albumin particles – is used to treat a range of cancers, including breast, ovarian and pancreatic. However, most of the therapy never reaches the tumor because immune cells in the liver, called Kupffer cells, aggressively clear the drug particles from the body.
Gut bacteria send chemical signals to those liver cells through molecules called bile acids, which are natural chemicals produced when gut bacteria process bile. When a commonly used antibiotic called metronidazole was administered to selectively reduce certain gut bacteria, bile acid levels dropped, causing the Kupffer cells to shift into a “quiet” state.
As a result, the Kupffer cells cleared fewer of the nanomedicine particles, allowing for extended circulation and increased accumulation in the tumor. This translated to significantly slowed tumor growth and prolonged survival in preclinical models of colon, breast, melanoma and pancreatic cancers.
