Exercise and Prebiotic Fiber Provide Gut Microbiota-Driven Benefit in a Survivor to Germ-Free Mouse Translational Model of Breast Cancer

SIMPLE SUMMARY: Breast cancer is the most common cancer in women worldwide. In recent years, the community of microbes that inhabit the intestinal tract, called the gut microbiota, has been shown to influence patient response to several cancer therapies. On the other hand, treatments such as chemotherapy can disrupt the resident gut microbiota and potentially contribute to poor health outcomes. Strategies to improve the composition of the gut microbiota include dietary and exercise interventions. While diet and exercise are already established as important for breast cancer prevention, during treatment, and for reducing recurrence, little is known about the impact of these factors on the gut microbiota in the context of breast cancer. Therefore, our aim was to examine the impact of exercise and diet on the gut microbiota in breast cancer. Our findings indicate that exercise and prebiotic fiber supplementation may provide benefits to individuals with breast cancer through advantageous gut microbial changes. Our findings of a potential adjuvant of exercise and prebiotics should inspire further mechanistic and clinical investigations. ABSTRACT: The gut microbiota plays a role in shaping overall host health and response to several cancer treatments. Factors, such as diet, exercise, and chemotherapy, can alter the gut microbiota. In the present study, the Alberta Cancer Exercise (ACE) program was investigated as a strategy to favorably modify the gut microbiota of breast cancer survivors who had received chemotherapy. Subsequently, the ability of post-exercise gut microbiota, alone or with prebiotic fiber supplementation, to influence breast cancer outcomes was interrogated using fecal microbiota transplant (FMT) in germ-free mice. While cancer survivors experienced little gut microbial change following ACE, in the mice, tumor volume trended consistently lower over time in mice colonized with post-exercise compared to pre-exercise microbiota with significant differences on days 16 and 22. Beta diversity analysis revealed that EO771 breast tumor cell injection and Paclitaxel chemotherapy altered the gut microbial communities in mice. Enrichment of potentially protective microbes was found in post-exercise microbiota groups. Tumors of mice colonized with post-exercise microbiota exhibited more favorable cytokine profiles, including decreased vascular endothelial growth factor (VEGF) levels. Beneficial microbial and molecular outcomes were augmented with prebiotic supplementation. Exercise and prebiotic fiber demonstrated adjuvant action, potentially via an enhanced anti-tumor immune response modulated by advantageous gut microbial shifts.