Exercise Helps Gut Microbes Quell Cancer

University of Pittsburgh scientists have discovered for the first time why exercise helps prevent cancer and fights existing tumors.  

According to the study published in the journal Cell, physical activity leads to beneficial changes in the gut microbiome. One of the key changes observed in mouse models was an increase in the production of formate, a small molecule generated by certain gut bacteria. This metabolite is believed to play a central role in the anti-cancer effects linked to exercise

Mice with an aggressive form of melanoma that exercised had smaller tumors and showed better survival compared to sedentary controls, an effect correlated with higher levels of formate in the gut. Exercising mice responded better to cancer immunotherapy treatments. The increase in formate and other microbiome changes are thought to boost the immune system’s effectiveness, making cancer therapies more successful.

When the scientists killed off the microbiome with antibiotics, exercise had no effect on cancer outcomes in the rodents, said lead author Catherine Phelps, emphasizing the importance of the gut microbiome. Using specialized tools, the researchers identified formate as the key player in the microbiota that helped quell cancer. Formate works by making CD8 T cells, the immune system’s chief cancer-fighting cells, more powerful.

In mouse models, daily formate significantly improved the outcomes for those with melanoma, adenocarcinoma, and lymphoma. Formate also improved the performance of immunotherapy drugs given to mice with melanoma.

Senior study author Marlies Meisel, assistant professor in the department of immunology at the Pittsburgh School of Medicine and her team also found that people with advanced melanoma who had high blood levels of formate had better survival rates than those with low levels of the metabolite when given immune checkpoint inhibitor therapy.

Further supporting the benefits of gut-derived metabolites, experiments with fecal microbiota transplantation (FMT) demonstrated that transferring the gut microbes from people with high or low levels of formate into mice with aggressive melanoma affected their tumors. The mice that received higher levels of formate had better tumor control.

 “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,” said Meisel.

These findings point to the emerging role of exercise as a complementary strategy to improve cancer therapies — partly by harnessing the power of gut microbes to produce beneficial compounds like formate.

Meisel and her team are investigating whether exercise-induced changes to the gut microbiome could benefit other diseases such as autoimmune disorders.