Exercise-linked gut changes may improve cancer treatment outcomes through immune response.
A recent study from the University of Pittsburgh has added new insight into how exercise might help fight cancer through a gut compound. The research, done in mice, found that physical activity changes the balance of bacteria in the gut in a way that improves how the immune system responds to tumors. More importantly, the team found a specific chemical, called formate, linked to these benefits. Formate, produced by gut microbes in active mice, helped shrink tumors and made cancer treatments more effective. These findings could offer new ways to support people going through immunotherapy.
Researchers began by studying two groups of mice—one group that exercised regularly and another that stayed still. The mice that ran daily developed smaller tumors and lived longer. But when the researchers removed gut bacteria from the equation—by either using germ-free mice or giving them antibiotics—those benefits disappeared. That result made it clear that the gut microbiome played a key role in how exercise helped.
To understand what was happening, the scientists looked closely at the chemical byproducts created by gut bacteria in exercised mice. They used a computer model to search for which substances might be responsible for the immune boost. The tool flagged formate, a compound made by bacteria during digestion. Further testing confirmed that formate increased the activity of cancer-fighting immune cells, especially CD8 T cells, which help destroy cancer cells.
Giving formate directly to mice through oral doses slowed tumor growth in several cancer types. It also made standard immune-based cancer treatments work better. When tested in different cancer models like melanoma and lymphoma, mice that received formate responded more strongly to therapy and had better chances of survival.
The team then looked at human patients with melanoma who were being treated with immunotherapy. Blood samples showed that those with higher levels of formate had better outcomes than those with lower levels. That link gave more weight to the idea that formate helps improve how the body fights cancer.
To explore this further, researchers used stool samples from patients with high and low formate levels. They transplanted the samples into mice with cancer. Mice that received transplants from high-formate donors had better tumor control and stronger immune activity. This experiment suggested that it’s not just the bacteria themselves, but what those bacteria produce, that matters for cancer treatment.
The study builds on earlier research about role of the gut compound in health and disease. While fecal transplants have already been explored as a way to help people respond better to immunotherapy, this study offers a clearer explanation for why some stool donors seem to work better than others.
Instead of focusing only on which bacteria are present, the findings suggest it may be more important to look at what those bacteria are doing—specifically, which chemicals they’re releasing into the body. That line of thinking could lead to more precise ways to predict treatment success or even design new supplements to boost cancer therapy.
Researchers now plan to test whether the same approach could help with other conditions linked to immune response, like autoimmune diseases. They also want to understand more about how exercise itself causes changes in the microbiome that lead to more formate.
While the results are based on animal models, they offer strong clues for future human research. The findings suggest that a simple compound made naturally in the gut might one day help support better cancer outcomes and improve the way treatments like immunotherapy work.
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Exercise improves cancer outcomes by shaping the gut microbiome
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