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区系组成对健康和福祉的重要性。乳房 癌症幸存者面临微生物群组成改变(生物失调)的风险增加，这可能有助于 癌症风险和疲劳等症状。动物模型和人体研究(包括我们的 研究小组)将锻炼与肠道微生物多样性的有利变化联系起来，丰富的 选择微生物，并产生有益的代谢物。因此，锻炼是一种很有前途的策略 逆转生态失调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，没有人登记癌症幸存者。运动训练对肠道微生物区系影响的测定 癌症幸存者的组成以及运动、肠道微生物区系组成、 疲劳可用于优化运动益处和开发新的治疗应用。vbl.做，做 因此，在疲惫的乳腺癌幸存者提供了机会，以减少痛苦的症状遭受 生活在美国的310万乳腺癌幸存者中的许多人。因此，我们建议一个随机的 乳腺癌幸存者疲乏和心肺功能不佳的对照试验。评估将 发生在基线、6周、12周和18周。我们的具体目标如下：主要目标：确定 持续12周有氧运动干预(侧重于改善心肺功能)的效果 适合度[VO2峰值])与肠道微生物区系组成的标准注意力控制(主要结果)进行比较 同时通过控制喂养使所有参与者的饮食标准化。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随着类杆菌(G)的增加、菌丝(P)的增加和减少 放线菌(O)和变形杆菌(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周将探索效果的持久性。第二目标：1)测试有氧运动训练是否 对肠道微生物区系组成的影响是通过炎症(白介素[IL])直接和/或间接介导的 -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)。 给定动态的大脑-肠道-微生物群轴，我们将通过对结果进行排序来测试中介关系 在评估期内采取措施，以便在前一周评估假想的调解人 收集粪便。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 通过肠道微生物区系组成的变化。我们将在每个项目中探索这些调解关系 通过在疲劳测量之前采集粪便样本来评估时间点。确定运动 对癌症幸存者肠道微生物区系组成的影响有可能确定增强的靶点 锻炼的好处，同时也为基于直觉的个性化锻炼处方提供基础数据 改善健康的微生物区系组成和肠道微生物区系组成的操作。

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.