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

肠道微生物组成在乳腺癌幸存者运动训练心理社会症状反应中的作用

基本信息

批准号：
9816846
负责人：
LAURA Q ROGERS
金额：
$ 61.63万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9816846
关键词：
Actinobacteria class Actinomycetales Aerobic Exercise Animal Model Animals Autonomic nervous system Bacteroides Biological Body Composition Breast Cancer survivor Cancer Survivor Clinical Collection Communities Control Groups Data Diet Dietary intake Distress Educational Intervention Enrollment Exercise Exercise stress test Fatigue Firmicutes Foundations Frequencies Future Health Health behavior Human Hydrocortisone Individual Inflammation Interleukin-10 Interleukin-6 Interleukins Intervention Link Malignant Neoplasms Measurement Mediating Mediation Mediator of activation protein Medical Meta-Analysis Microbe Modeling Nonpharmacologic Therapy Outcome Outcome Measure Participant Pathway interactions Patient Outcomes Assessments Personal Satisfaction Phase II Clinical Trials Physical activity Physiological Production Proteobacteria Publishing Quality of life Randomized Randomized Controlled Trials Recommendation Reporting Research Risk Role Sampling Standardization Symptoms Testing Therapeutic Time Translational Research Work attentional control base beta diversity breast cancer diagnosis cancer diagnosis cancer recurrence cancer risk cancer therapy cardiorespiratory fitness clinical application clinically significant design disability dysbiosis energy balance exercise intervention exercise prescription exercise training feeding gut bacteria gut microbes gut microbiota heart rate variability human study hypothalamic-pituitary-adrenal axis improved microbial microbiome microbiota microbiota-gut-brain axis mortality novel therapeutics post intervention primary outcome psychosocial randomized trial response social attention treatment strategy

项目摘要

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.

越来越多的证据支持肠道微生物群组成对乳房健康的重要性。癌症幸存者微生物群组成改变（菌群失调）的风险增加，这可能会导致癌症风险和疲劳等症状动物模型和人体研究（包括我们的工作）。研究小组）将运动与肠道微生物多样性的有利变化联系起来，肠道微生物的丰富性选择微生物并产生有益的代谢物因此，运动是一种有前途的策略。扭转生态失调，但只有一项人体研究使用了随机设计，没有一项严格控制饮食，并且没有人招募癌症幸存者来确定运动训练对肠道微生物群的影响。癌症幸存者的组成以及运动、肠道微生物群组成、和疲劳可用于优化运动益处并开发新的治疗应用。因此，为疲劳的乳腺癌幸存者提供了减少乳腺癌幸存者所遭受的痛苦症状的机会生活在美国的 310 万乳腺癌幸存者中的许多人因此，我们提出了一项随机对患有疲劳和心肺健康状况不佳的乳腺癌幸存者进行对照试验。发生在基线、6 周、12 周和 18 周时。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身[峰值摄氧量]）与肠道微生物群组成的标准注意力控制相比（主要结果）同时根据我们的初步工作，通过控制喂养来标准化所有参与者的饮食。研究发现，与对照组相比，有氧运动训练组将表现出显着的肠道微生物多样性差异：拟杆菌 (g) 增加、厚壁菌门 (p) 增加、减少放线菌 (o) 和变形菌 (p) 第 12 周是我们在第 6 周将探索的主要时间点；第 18 周将探讨效果的持久性：1) 测试有氧运动训练是否有效。对肠道微生物群组成的影响是通过炎症直接和/或间接介导的（白细胞介素 [IL] – 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评估期内采取的措施，以便在评估之前一周对跟踪调解员进行评估 2) 测试有氧运动训练对疲劳的影响是否是直接和/或间接介导的。我们将通过肠道微生物群组成的变化来探索这些中介关系。通过在确定运动量之前收集粪便样本来评估时间点。对癌症幸存者肠道微生物群组成的影响有可能确定增强的目标运动益处，同时还为基于肠道的个性化运动处方提供基础数据微生物群组成和肠道微生物群组成调控以改善健康。