Role of gut microbe composition in psychosocial symptom response to exercise training in breast cancer survivors

越来越多的证据支持肠道微生物群组成对健康和福祉的重要性。乳腺 癌症幸存者改变微生物群组成（生态失调）的风险增加，这可能有助于 癌症风险和疲劳等症状。动物模型和人类研究（包括我们的工作） 研究小组）已经将运动与肠道微生物多样性的有利变化联系起来， 选择微生物和生产有益的代谢物。因此，锻炼是一种很有前途的策略， 然而，只有一项人类研究使用了随机设计，没有一项严格控制 饮食，没有人招募癌症幸存者。确定运动训练对肠道微生物群的影响 癌症幸存者的肠道菌群组成以及运动，肠道微生物群组成， 和疲劳可以应用于优化锻炼益处和开发新的治疗应用。做 因此，对于疲劳的乳腺癌幸存者来说， 许多310万乳腺癌幸存者生活在美国，因此，我们提出了一个随机的， 在疲劳和低心肺适应性的乳腺癌幸存者中进行对照试验。评估将 在基线、6周、12周和18周时发生。我们的具体目标如下：主要目标：确定 渐进式12周有氧运动训练干预的效果（重点是改善心肺功能） 健康[峰值VO2]）与肠道微生物群组成的标准注意力控制相比（主要结局） 同时对所有参与者进行标准化饮食控制喂养。根据我们的初步工作，我们 假设与对照组相比，有氧运动训练组将表现出显著的 肠道微生物多样性的差异，增加拟杆菌（g），增加厚壁菌门（p），和减少 放线菌目（o）和变形菌门（p）。第12周是我们的主要时间点;第6周将探索中期 变化和第18周将探讨影响的持久性。次要目的：1）测试有氧运动训练是否 对肠道微生物群组成的影响直接和/或间接通过炎症（白细胞介素[IL]）介导 - 6，IL-10），自主神经系统（心率变异性），或下丘脑-垂体-肾上腺轴（皮质醇）。 考虑到动态的脑-肠-微生物群轴，我们将通过对结果进行排序来测试中介关系 在评估期内进行测量，以便在评估前一周评估假设的介质。 粪便收集2)测试有氧运动训练对疲劳的影响是否直接和/或间接介导 通过肠道微生物群组成的变化。我们将探讨这些中介关系， 通过在疲劳测量之前收集粪便样品来确定评估时间点。决定性运动 对癌症幸存者肠道微生物群组成的影响有可能确定增强 锻炼的好处，同时也提供了基于肠道的个性化运动处方的基础数据， 微生物群组成和肠道微生物群组成操纵以改善健康。

Growing evidence supports the importance of the gut microbiota composition for health and well-being. Breast cancer survivors are at increased risk for altered microbiota composition (dysbiosis) which may contribute to cancer risk and symptoms such as fatigue. Animal models and human studies (including work by our investigative team) have linked exercise with favorable changes in gut microbial diversity, an abundance of select microbes, and production of beneficial metabolites. As such, exercise is a promising strategy for reversing dysbiosis yet only one human study has used a randomized design, none have strictly controlled diet, and none have enrolled cancer survivors. Determining exercise training effects on gut microbiota composition in cancer survivors and potential mechanistic links between exercise, gut microbiota composition, and fatigue can be applied to optimizing exercise benefits and developing new therapeutic applications. Doing so in fatigued breast cancer survivors provides the opportunity to reduce a distressing symptom suffered by many of the 3.1 million breast cancers survivors living in the U.S. Therefore, we propose a randomized controlled trial among breast cancer survivors with fatigue and low cardiorespiratory fitness. Assessments will occur at baseline, 6 weeks, 12 weeks, and 18 weeks. Our specific aims are as follows: Primary aim: Determine effects of a progressive 12-week aerobic exercise training intervention (focused on improving cardiorespiratory fitness [peak VO2]) compared to standard attention control on gut microbiota composition (primary outcome) while standardizing diet across all participants with controlled feeding. Based on our preliminary work, we hypothesize that compared to control, the aerobic exercise training group will demonstrate significant differences in gut microbial diversity with increased Bacteroides (g), increased Firmicutes (p), and decreased Actinomycetales (o) and Proteobacteria (p). Week 12 is our primary time point; week 6 will explore interim changes and week 18 will explore durability of effects. Secondary aim: 1) Test if the aerobic exercise training effect on gut microbiota composition is directly and/or indirectly mediated through inflammation (interleukin [IL] – 6, IL – 10), autonomic nervous system (heart rate variability), or hypothalamic-pituitary-adrenal axis (cortisol). Given the dynamic brain-gut-microbiota axis, we will test mediation relationships by ordering our outcome measures within the assessment period such that hypothesized mediators are assessed in the week prior to the fecal collection. 2) Test if the aerobic exercise training effect on fatigue is directly and/or indirectly mediated through changes in the gut microbiota composition. We will explore these mediation relationships within each assessment time points by collecting the fecal sample prior to fatigue measurement. Determining exercise effects on gut microbiota composition in cancer survivors holds the potential to identify targets for enhancing exercise benefits while also providing foundational data for personalized exercise prescriptions based on gut microbiota composition and gut microbiota composition manipulation for improved health.