Fatigue and the Gut Microbiome of Patients Receiving Chemoradiotherapy for Rectal Cancer

摘要/项目摘要 疲劳是化疗放射（CRT）最令人痛苦和最常见的副作用之一， 78%的直肠癌患者抱怨CRT期间严重疲劳。虽然病因和相关的 CRT治疗期间癌症相关疲劳的机制仍不清楚，有人提出， 生态失调（肠道中肠道微生物群的不平衡）可能会导致疲劳恶化， 患者的盆腔CRT。本研究将有助于解决症状研究中的知识缺口， 健康文献，提供与以下关系相关的生物/肠道微生物过程的初步证据： CRT之间，生态失调，并在直肠癌人群疲劳，使更多的创新和个性化 可以制定干预措施。本研究以化疗相关方模型为指导 方面的影响.培训计划旨在让申请人扩大她的理论知识和技能， 症状表型和进行生物行为和微生物组研究，以满足NRSA 培训目标，并启动作为一个独立的护士科学家的职业生涯。经验丰富的科学家团队 将领导研究培训计划，以实现以下目标：（1）提高她对 与CRT诱导的肠道微生物组生态失调和疲劳之间的拟议机制相关的科学;（2） 增加她对CRT相关疲劳表型特征的理解， 和临床数据，以及微生物组数据收集技术和分析， 方法;（3）获得微生物组研究（包括粪便）方面的全面培训和知识 收集和处理，细菌16 S rRNA扩增子测序，鸟枪宏基因组学分析， 微生物组衍生的宏基因组学数据的解释;和（4）提高科学写作技能和建设 与生物行为/症状管理/微生物组研究领域的专家合作， 在高影响力的同行评审期刊上成功发表，并提交有竞争力的资助申请。的 培训计划为期24个月，包括六个核心领域：教学;跨学科研讨会; 指导;实验室培训;研究;和传播。拟议研究的具体目标是： 目的1：检查在CRT治疗过程中，成人肠道微生物组多样性的时间变化， 局限性直肠癌目的1a：研究CRT期间的疲劳强度是否与 肠道微生物多样性在治疗过程中发生变化。目标2：检查 在CRT治疗过程中患有局限性直肠癌的成年人的特定肠道微生物的丰度。目的 2a：研究肠道微生物丰度变化与疲劳变化之间的关联 CRT治疗过程中的评分。通过对肠道与人类免疫系统之间关系的创新性研究， CRT期间的微生物变化和疲劳症状，这项研究符合NINR的使命， 研究以病人为中心的生物行为研究，促进健康和提高生活质量。

Abstract/Project Summary Fatigue is one of the most distressing and commonly reported side effects of chemo-radiation (CRT), with up to 78% of rectal cancer patients complaining of severe fatigue during CRT. While the etiology and associated mechanism of the cancer-related fatigue during CRT treatment remain elusive, it has been suggested that dysbiosis (an imbalance in the intestinal microbiota in the gut) may contribute to worsening of fatigue during a patients’ pelvic CRT. This study will contribute to address the knowledge gap in symptom research and the health literature by providing initial evidence of the biologic/gut microbial processes related to the relationship among CRT, dysbiosis, and fatigue in the rectal cancer population, so that more innovative and individualized interventions can be developed. The proposed research is guided by a model of chemotherapy-related side effects. The training plan was designed to allow the applicant to expand her theoretical knowledge and skills in symptom phenotyping and conducting bio-behavioral and microbiome research in order to meet the NRSA traineeship goals and launch a career as an independent nurse scientists. An experienced team of scientists will lead the research training plan as related to the following objectives: (1) to enhance her understanding of the science related to the proposed mechanism linking CRT-induced gut microbiome dysbiosis and fatigue; (2) to increase her understanding of the characterization of CRT-related fatigue phenotypes with patient biological and clinical data, and microbiome data collection techniques and analysis through a bedside-to-bench approach; (3) to obtain comprehensive training and knowledge in microbiome research including stool collection and processing, bacterial 16S rRNA amplicon sequencing, shotgun metagenomics analysis and interpretation of microbiome-derived metagenomics data; and (4) to improve scientific writing skills and building collaborations with experts in the field of bio-behavioral/symptom management/microbiome research to successfully publish in high-impact, peer-reviewed journals, and submit competitive grant applications. The training plan is for twenty four months and includes six core areas: didactic; interdisciplinary seminars; mentorship; laboratory training; research; and dissemination. The specific aims of the proposed study are to: Aim 1: Examine the temporal changes in diversity of the gut microbiome over the course of CRT of adults with localized rectal cancers. Aim 1a: To investigate whether the intensity of fatigue during CRT is associated with the gut microbial diversity changes during the course of treatment. Aim 2: Examine the temporal changes on the abundances of specific gut microbes of adults with localized rectal cancers over the course of CRT. Aim 2a: To investigate the associations between changes in the gut microbial abundance with changes in fatigue scores during the course of CRT. By focusing on the innovative investigation of the relationship between gut microbial changes and fatigue symptoms during CRT, this study aligns with the mission of NINR calling for studies on patient-centered bio-behavioral research that promote health and enhanced quality of life.