Gut Microbes as a Key to Enhancing Cancer Immunotherapy Response Through Exercise

Recent research from the University of Pittsburgh reveals that gut microbes play a crucial role in how exercise improves cancer outcomes and boosts the effectiveness of immunotherapy. In a study published in Cell, scientists demonstrated that exercise in mice leads to changes in the gut microbiome, specifically increasing the production of a compound called formate. This metabolite, produced by bacteria in the gut during exercise, was associated with better tumor control and improved survival rates in mice with melanoma, lymphoma, and adenocarcinoma.

The study found that the beneficial effects of exercise vanish when the gut microbiome is eliminated, such as through antibiotics or in germ-free mice, emphasizing the microbiome's vital role. Further analysis identified formate as the key metabolite mediating immune enhancement. When administered orally to mice, formate increased the activity of CD8 T cells, the immune system’s primary cancer-fighting cells, leading to reduced tumor growth and improved response to immune checkpoint inhibitors.

In human studies, melanoma patients with higher blood levels of formate experienced longer progression-free survival during immunotherapy. Additionally, fecal microbiota transplants (FMT) from humans with high formate levels into mice resulted in improved tumor control and immune response, suggesting potential for microbiome-based therapies.

This research suggests that exercise-induced changes in the gut microbiome could be targeted to develop new treatments for cancer and possibly other diseases. Future investigations are ongoing to explore how exercise influences the microbiome and how microbiota-derived metabolites like formate could be used as adjuvants to enhance immunotherapy effectiveness, particularly in patients who currently do not respond well.

Source: https://medicalxpress.com/news/2025-07-gut-microbes-key-boosts-cancer.html