Imagine a drug that keeps cancer in check but leaves patients with burning pain in their hands and feet, and nausea that makes eating feel impossible. This is the reality for many multiple myeloma patients taking bortezomib, one of the most widely used treatments for this blood cancer. Now, researchers at the South Australian Health and Medical Research Institute (SAHMRI) in Adelaide have uncovered something remarkable — these debilitating side effects might be tied to the bacteria living in our guts.
Dr. Jacqui Scott and Associate Professor Hannah Wardill led a team that developed a new way to study how bortezomib affects the body. Using specialized mice, the researchers found that the drug triggers changes in the way nerves and the immune system communicate, causing both nerve damage and gut problems.
But the most exciting discovery came when the team studied mice raised without any gut bacteria — so-called germ-free mice. In these animals, the drug's side effects almost entirely disappeared.
"We have known for a long time that bortezomib damages nerves, but this understanding has been almost exclusively focused on peripheral nerves, like those in the hands and feet," Dr. Scott said. "Using this model, we were able to show that similar mechanisms occur in the gut, providing the first evidence to help us explain why bortezomib causes debilitating gut problems."
The team, which included four SAHMRI research groups working together, made another surprising finding: when they restored the gut bacteria in these mice, the side effects did not come back. This suggests the initial absence of bacteria had somehow changed the animals' biology in a lasting way.
"What makes our findings unique is that when we restore the microbiome, the side effects do not return," Dr. Scott said. "We're now trying to identify why that is and whether we can translate this to patients."
Dr. Krzysztof Mrozik, a senior researcher at SAHMRI and Adelaide University, said the collaboration between experts in cancer support, pain research, microbiome science, and immunology was key to the breakthrough. "We've been able to gain a completely new perspective on how these side effects develop," he said.
The researchers hope their findings, published in the Journal of Neuroinflammation, will lead to new ways to help cancer patients stay on life-saving treatments for longer.