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：
10458670
负责人：
Jinbing Bai
金额：
$ 24.15万
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 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10458670
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.

抽象的人体的寄主是数万亿微生物，这是人体数量的10倍细胞。人类相关的微生物及其基因组被称为“人类微生物” 90％的微生物生活在胃肠道（GI）中，平均抑制了500种高脚齿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shot弹枪宏基因组学分析），最新进步哈斯（Hass Hass）来阐述肠道微生物组的关键角色在健康和疾病中玩。微生物组与癌变，化学治疗代谢和与治疗相关的症状标记有关。癌症肠道微波经科学的当前科学状态直到最近才从动物模型开始成人，尚未在被诊断和治疗的癌症的Cildren中得到很好的研究，或与癌症的关联与治疗相关的毒性。与癌症治疗相关的GI和心理学症状相关。 K99/R00建议将执行三个具体目标：AIM 1将以肠道的纵向变化来表征与使用16S rRNA的健康Sivings相比，7-18岁的实体瘤儿童的微生物组在K99阶段进行测序； R00阶段将重点放在两个特定目标上患有癌症和健康兄弟姐妹儿童的物种和病原体跟随16S rRNA基因进行整体测序基因组shot弹枪分析；整个化学疗法的儿童的心理学症状基于一个概念模型微生物组 - 脑轴，使用16S rRNA测序和shot弹枪元素学分析。癌症儿童，当前和未来培训，研究指导和我们的发现，动机和非常支持的研究环境，我将准备领导这一拟议项目。将有助于确定癌症治疗症状的潜在生物学机制，并将导致潜在的干预措施（例如，益生元和益生菌补充）尖端的方法，例如16S rRNA测序，大数据Qiime 2分析和全基因组shot弹枪核能学与癌症治疗相关的gi和心理尿液Lolololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololol很多情ololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololololol 一下，，，. 概念微生物组 - 脑轴框架。我学习新方法并发展自己的专业技能，以成功地过渡到独立护士科学家专注于小儿肿瘤学症状科学的生物心理社会机制（即肠道微波经）。