The Impact of Exercise on Gut Microbiota in a Survivor to Germ-free Mouse Translational Model of Breast Cancer

Breast cancer is the leading cause of global cancer incidence. Strategies to improve breast cancer treatment and health outcomes in survivors are needed to decrease mortality, mitigate side effects, and prevent recurrence. The gut microbiota is altered in individuals with breast cancer, can be affected by treatments such as chemotherapy, and plays a role in response to cancer treatments. It may be modified by environmental factors such as dietary components and exercise. 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 undergone chemotherapy. In a follow-up germ-free mouse study, the ability of exercise-responsive gut microbiota, alone or with prebiotic fiber supplementation, to alter tumor growth was interrogated using fecal microbiota transfer (FMT). In the cancer survivors, there was a significant enrichment in Dialister, Oscillospiraceae, and Paraprevotella following exercise (p < 0.01). In the germ-free mice, tumor volume trended consistently lower over time in the groups colonized with post-exercise gut microbiota compared to the group colonized with pre-exercise gut microbiota, with statistically significant differences found on day 16 and day 22. Tumor volume was further suppressed with prebiotic fiber supplementation. Gut microbial alpha and beta diversity differed across groups. Beta diversity and differential abundance analyses revealed that both the tumor cell injection and chemotherapy altered the gut microbial community in the mice. A potentially beneficial enhancement of Parasutterella and Lachnospiraceae and depletion of Anaerostipes and Ruminococcus gnavus was identified on day 22 in the group receiving prebiotic. Cytokine analysis of tumor tissue and serum indicated that the influence of the various FMTs resulted in distinct tumor microenvironments. The tumors of mice colonized with exercise-responsive microbiota exhibited lower levels of angiogenic VEGF among other markers, and greater levels of cytokines previously associated with positive Paclitaxel response. This was augmented with prebiotic supplementation. Exercise and prebiotic demonstrated potential to enhance anti-tumor immunity through advantageous gut microbiota modulation in breast cancer populations and should be further explored as adjuvants

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

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

The Gut Microbiota: A Potential Gateway to Improved Health Outcomes in Breast Cancer Treatment and Survivorship

Breast cancer is the most frequently diagnosed cancer in women worldwide. The disease and its treatments exert profound effects on an individual&rsquo;s physical and mental health. There are many factors that impact an individual&rsquo;s risk of developing breast cancer, their response to treatments, and their risk of recurrence. The community of microorganisms inhabiting the gastrointestinal tract, the gut microbiota, affects human health through metabolic, neural, and endocrine signaling, and immune activity. It is through these mechanisms that the gut microbiota appears to influence breast cancer risk, response to treatment, and recurrence. A disrupted gut microbiota or state of &lsquo;dysbiosis&rsquo; can contribute to a biological environment associated with higher risk for cancer development as well as contribute to negative treatment side-effects. Many cancer treatments have been shown to shift the gut microbiota toward dysbiosis; however, the microbiota can also be positively manipulated through diet, prebiotic and probiotic supplementation, and exercise. The objective of this review is to provide an overview of the current understanding of the relationship between the gut microbiota and breast cancer and to highlight potential strategies for modulation of the gut microbiota that could lead to improved clinical outcomes and overall health in this population

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

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