Exploring the Microbiome-Gut-Brain Axis in Psychoneurological Symptoms for Children with Solid Tumors

探索实体瘤儿童心理神经症状中的微生物组-肠-脑轴

基本信息

批准号：
10252956
负责人：
Jinbing Bai
金额：
$ 24.53万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-29 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10252956
关键词：
16S ribosomal RNA sequencing 5 year old Actinobacteria class Acute Adult Adverse event Affect Aftercare Animal Model Antibiotics Anxiety Bacteroides Bacteroidetes Bifidobacterium Big Data Biodiversity Biological Body mass index Brain Cells Chemotherapy-Oncologic Procedure Child Childhood Collection Common Terminology Criteria for Adverse Events Communities Data Development Diagnosis Diarrhea Diet Disease Ecosystem Enterococcus Environment Ethnic Origin Etoposide Fatigue Firmicutes Future Gastrointestinal tract structure Genome Germ Cell Cancers Grant Health High-Throughput Nucleotide Sequencing Hormonal Human Human Microbiome Human body Immune Impaired cognition Inflammation Intervention Intestines Lactobacillus Lead Learning Life Malignant Childhood Neoplasm Malignant Neoplasms Measures Mental Depression Mentors Metabolism Metagenomics Methotrexate Microbe Modeling Motivation Mucositis Nurses Outcome Pain Pathogenicity Pathologic Pathway interactions Patient Outcomes Assessments Pediatric Oncology Pharmaceutical Preparations Phase Play Precision Health Prevotella Probiotics Quality of life RNA, Ribosomal, 16S Race Reporting Research Research Project Grants Ribosomal RNA Role Science Scientist Shotguns Siblings Signal Transduction Solid Neoplasm Strategic Planning Symptoms Technology Testing Time Toxic effect Training Treatment-Related Cancer Treatment-related toxicity Work active method acute symptom aged base bioinformatics tool biopsychosocial cancer diagnosis cancer therapy carcinogenesis chemotherapy combat commensal microbes design dosage dysbiosis exercise capacity gastrointestinal gastrointestinal symptom gut dysbiosis gut microbiome gut-brain axis improved innovation irinotecan metagenomic sequencing microbial microbial community microbial genome novel strategies pathogen pediatric patients potential biomarker prebiotics prevent probiotic supplementation protective effect public health relevance reduce symptoms relating to nervous system response sarcoma sex skills survivorship symptom cluster symptom science treatment duration tumor whole genome

项目摘要

ABSTRACT The human body hosts tens of trillions of microbes, which number is 10 times greater than the number of human body cells. The collection of these human-associated microbes and their genomes is called the “human microbiome”. More than 90% of these microbes live in the gastrointestinal (GI) tract, representing 500 species on average. With the development of high-throughput sequencing technology and bioinformatics tools (e.g., 16S ribosomal RNA or 16S rRNA sequencing and shotgun metagenomics analysis), recent progress has been made to elaborate the critical role that the gut microbiome is playing in human health and disease. A significant disruption (dysbiosis) of the composition and function of the gut microbiome is associated with carcinogenesis, chemotherapeutic metabolism, and treatment-related symptom toxicities. The current state of the science on the gut microbiome in cancer has been only recently starting in animal models and adults and has not been well investigated in children diagnosed and treated for cancer, nor with associations with cancer treatment-related toxicities. This proposed study will explore the hypothesis that dysbiosis of the gut microbiome is associated with cancer treatment-related GI and psychoneurological symptoms. In order to test our hypothesis, this K99/R00 proposal will execute three specific aims: Aim 1 will characterize the longitudinal changes of the gut microbiome in children aged 7-18 years with solid tumors as compared with their healthy siblings using 16S rRNA sequencing during the K99 Phase; the R00 Phase will focus on two specific aims: Aim 2 will screen specific microbial species and pathogens in children with cancer and healthy siblings following 16S rRNA gene sequencing using whole- genome shotgun metagenomics analysis; and Aim 3 will examine associations between the gut microbiome and GI and psychoneurological symptoms in children with solid tumors throughout chemotherapy based on a conceptual model of the microbiome-gut-brain axis, using 16S rRNA sequencing and shotgun metagenomics analysis. With respect to my expertise and productive research projects in children with cancer, current and future trainings, research mentoring and motivations, and the very supportive research environment, I will be prepared to lead this proposed project. Our findings will help identify potential biological mechanisms underlying symptoms of cancer treatment, and will lead to potentially precise targets for interventions (e.g., prebiotic and probiotic supplementations). This proposal includes cutting-edge approaches such as 16s rRNA sequencing, big data QIIME 2 analytics and whole-genome shotgun metagenomics with the innovative use in cancer treatment-related GI and psychoneurological symptoms and a testable conceptual microbiome-gut-brain axis framework. In summary, the K99/R00 grant represents a unique opportunity for me to learn new approaches and develop my professional skills to successfully transition into an independent nurse scientist focusing on the biopsychosocial mechanisms (i.e., gut microbiome) of symptom science in pediatric oncology.

抽象的人体拥有数十万亿微生物，其数量是人体数量的10倍这些与人类相关的微生物及其基因组的集合被称为“人类微生物组”。这些微生物中 90% 生活在胃肠道 (GI) 中，平均有 500 种。高通量测序技术和生物信息学工具（例如 16S 核糖体 RNA 或 16S rRNA 测序）和鸟枪法宏基因组学分析），最近在阐述肠道微生物组的关键作用方面取得了进展肠道的组成和功能受到严重破坏（生态失调）。微生物组与致癌、化疗代谢和治疗相关症状毒性有关。关于癌症肠道微生物群的科学现状最近才开始在动物模型中进行，成人，并且尚未在诊断和治疗癌症的儿童中进行充分的研究，也没有对与癌症的关联进行深入研究这项拟议的研究将探讨肠道微生物菌群失调的假设。与心理癌症治疗相关的胃肠道和神经系统症状有关。 K99/R00 提案将执行三个具体目标：目标 1 将描述肠道的纵向变化使用 16S rRNA 将 7-18 岁实体瘤儿童的微生物组与其健康兄弟姐妹进行比较 K99 阶段的测序；R00 阶段将重点关注两个具体目标：目标 2 将筛选特定微生物使用全 16S rRNA 基因测序后，研究癌症儿童和健康兄弟姐妹的物种和病原体基因组霰弹枪宏基因组学分析；目标 3 将检查肠道微生物组与胃肠道之间的关联基于概念模型的实体瘤儿童在整个化疗过程中的心理神经症状微生物组-肠-脑轴，使用 16S rRNA 测序和鸟枪法宏基因组学分析。癌症儿童方面的专业知识和富有成效的研究项目、当前和未来的培训、研究指导和动机以及非常支持的研究环境，我将准备好领导这个拟议的项目我们的研究结果。将有助于识别癌症治疗症状背后的潜在生物学机制，并将导致该提案包括潜在的精确干预目标（例如益生元和益生菌补充剂）。尖端方法，如 16s rRNA 测序、大数据 QIIME 2 分析和全基因组鸟枪法宏基因组学在癌症治疗相关的胃肠道和心理神经症状方面具有创新用途，并且具有可测试的总之，K99/R00 资助代表了一个独特的机会。我学习新方法并发展我的专业技能，以成功过渡为独立护士专注于儿科肿瘤学症状科学的生物心理社会机制（即肠道微生物组）的科学家。