Exercise helps fight cancer by changing gut microbes

Everyone knows exercise is good. It keeps hearts healthy, muscles strong, and minds calm. But what if it could also help fight cancer?

Scientists at the University of Pittsburgh found something surprising. Exercise doesn’t just benefit the body. It also changes tiny microbes living inside us. These changes can make cancer treatments work better.

The study connects three things: exercise, the gut microbiome, and cancer treatment success. For years, researchers knew exercise helped cancer therapies. They also knew exercise altered gut bacteria. But no one connected those dots before.

Exercise changes gut to fight cancer

“We already knew that exercise increases the effectiveness of cancer immunotherapies, and we separately knew that exercise changes the microbiome in mice and humans,” said Dr. Marlies Meisel, senior author of the research paper.

“This study connects those dots by showing how exercise-induced changes in the gut microbiome boost the immune system and enhance immunotherapy efficiency via formate. These findings open the door to new therapeutic strategies targeting the microbiome.”

In simpler terms, exercise reshapes the gut in ways that make cancer drugs work better. The team started by comparing two groups of mice. One group got plenty of exercise for four weeks, while the other group did not move much at all.

When cancer cells were introduced, the differences from exercise became clear. The exercise group had smaller cancer tumors. They also lived longer.

Gut microbes drive cancer protection

In a surprising twist, when the researchers wiped out the mice’s gut bacteria using antibiotics, exercise no longer helped.

“When we removed microbes from the equation, exercise no longer had any effect on cancer outcomes in mice,” said Catherine Phelps, lead author of the study.

“We were surprised to see such a clear signal that the beneficial effects of exercise were due to the microbiome.”

That discovery flipped everything upside down. It wasn’t just exercise itself. It was the gut bacteria that responded to exercise and made the difference.

Gut compound linked to exercise

Next, the team looked deeper. What was it about those bacteria that helped? It wasn’t the bacteria alone. It was their chemical products.

The scientists used a machine learning tool called SLIDE to hunt for answers. SLIDE identified a surprising hero. That hero was formate.

This simple molecule, made by gut microbes, changed everything. Formate supercharged immune cells known as CD8 T cells. These are the body’s main cancer fighters.

When mice were given formate directly, their tumors shrank. They also survived longer. And when researchers paired formate with cancer immunotherapy, results improved even more.

“It’s really exciting to identify a specific bacterial metabolite that mimicked the effects of exercise in mice,” said Meisel.

“In the future, formate could potentially be investigated as an adjuvant therapy to improve the efficacy of immune checkpoint inhibitors in non-responders.”

Research on cancer and exercise

Mouse studies on exercise and cancer were exciting, but humans matter more. So, the researchers studied cancer patients with advanced melanoma.

The researchers checked the patients’ blood for formate. Those with more formate had better cancer treatment results.

Then came another clever test. The team collected stool samples from these patients. The samples went to mice with melanoma.

Some mice received stool from patients with high formate levels. Others got stool from patients with low formate.

The cancer outcome was clear. Mice that received high-formate samples from exercise-linked donors fought cancer better. Their immune systems kicked into gear.

Some gut microbes work better

Fecal microbial transplants, or FMT, are already being studied to help cancer treatments. But nobody fully understands why some donor samples work better than others.

“We want to describe metabolic biomarkers to identify FMT super donors because that’s really a black box,” said Meisel.

“Currently everyone focuses on bacterial species, but our research suggests that it’s not just about which microbes are present, but what they are doing and which metabolites they are producing.”

That’s a big shift in thinking. Instead of worrying about which bacteria live in the gut, it may be smarter to focus on what chemicals those bacteria make.

New ways exercise may help fight cancer

This research opens many new doors. Meisel and her team now wonder if exercise-triggered gut changes can help with other diseases too.

The researchers are especially curious about autoimmune disorders. They also want to know how exercise actually transforms the gut microbiome in the first place.

One thing is certain. Exercise is more powerful than it seems in cancer care. It doesn’t just move muscles or burn calories. It also changes gut chemistry, which may someday improve cancer treatments.

The study is published in the journal Cell.

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