Immune Dysregulation in Eating Disorders (ID-ED)

饮食失调中的免疫失调 (ID-ED)

基本信息

批准号：
10588176
负责人：
Brooks Barrett Brodrick
金额：
$ 19.44万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10588176
关键词：
Address Adult Ambulatory Care Animal Model Anorexia Nervosa Award Behavior Behavior Disorders Behavioral Symptoms Binge Eating Biological Markers Biometry Board Certification Body Weight Brain Clinical Complex Data Development Disease Eating Behavior Eating Disorders Energy Intake Exercise Experimental Designs Female Foundations Functional disorder Future Gastrointestinal Physiology Genomic DNA Goals Human Immune Immune response Immune system Immunological Models Immunology Individual Inflammation Inflammatory Inpatients Interleukin-1 beta Interleukin-6 Internist K-Series Research Career Programs Knowledge Link Lipopolysaccharides Literature Measures Mediating Mental Depression Mental disorders Mentors Mentorship Meta-Analysis Metagenomics Molecular Neurobehavioral Manifestations Occupations Outpatients Participant Pathway interactions Patients Peripheral Blood Mononuclear Cell Persons Phenotype Physiological Physiological Processes Physiology Post-Traumatic Stress Disorders Production Psychopathology Recovery Reporting Research Research Methodology Research Project Grants Sampling Science Science Enrichment Scientist Secure Self Perception Shapes Shotgun Sequencing Site Specimen Stratification Symptoms System TNF gene Taxonomy Training Translational Research Weight Woman career development cohort cytokine design dysbiosis gastrointestinal function gut microbes gut microbiome gut microbiota immune function immunological status improved indexing inflammatory marker innovation intestinal epithelium medical complication microbiome composition neuroimmunology novel strategies personalized medicine purge rRNA Genes responsible research conduct systems research translational physician

项目摘要

Anorexia nervosa (AN) is a psychiatric illness characterized by both distorted self-image and a restriction of energy intake relative to requirements, leading to significantly low body weight, and frequently resulting in severe medical complications. As such, numerous physiological changes in people with AN have been observed, including differences in both immunological and gastrointestinal function during the disease. However, these changes have not yet been related to the cognitive and behavioral symptoms observed during AN. This K23 Mentored Career Development Award proposal is a first step to address this gap in the literature. Our proposed research project will evaluate both immune dysregulation and gut microbiome composition in women with AN and healthy comparison participants. In Aim 1, we characterize the molecular components of inflammation by assessing both basal and innate cytokine production capacity. In Aim 2, we evaluate the composition of the gut microbiome and its relationship to eating disorder symptoms. Lastly we will explore (Aim 3) whether alterations in gut microbiome composition correlate with inflammatory marker levels. The career development portion of this award provides the PI with detailed training in 1) gut microbiome-immune system research; 2) psychopathology research methods necessary to conduct independent research investigating biomarkers in eating disorders; 3) translational science design, implementation and management; and 4) responsible conduct of research. An expert team of mentors and advisors will oversee both research and training aims, including an on-site primary mentor with expertise in eating disorders and translational science, Dr. Carrie McAdams, and an on-site co-mentor with expertise in how gut microbiome modulates host immune responses, Dr. Andrew Koh. Dr. Cynthia Bulik, a scientific advisor, will provide mentorship on relating biomarkers with complex human behaviors seen in psychiatric illness. Two additional scientific advisors, Dr. Robert Haley (expertise in biostatistics in relation to neuroimmunology) and Dr. Larry Borish (expertise on immune function and inflammatory pathways) complete the mentorship team. The research and training outlined in this proposal will provide crucial formal and experiential training to allow the PI, a board certified internist with a strong research background in gastrointestinal physiology and immunology, to develop into an independent translational physician-scientist.

神经性厌食症（AN）是一种精神病，以扭曲的自我形象和A为特征相对于要求的能量摄入量的限制，导致体重明显低，并且经常导致严重的医疗并发症。因此，许多生理变化已经观察到患有一个人的人，包括免疫学和疾病期间的胃肠道功能。但是，这些变化尚未相关在An期间观察到的认知和行为症状。这个K23的指导职业发展奖提案是解决文献差距的第一步。我们提出的研究项目将评估免疫失调和肠道微生物组组成在患有健康比较参与者的女性中。在AIM 1中，我们描述了通过评估基础和先天细胞因子的产生，炎症的分子成分容量。在AIM 2中，我们评估了肠道微生物组的组成及其与饮食失调症状。最后，我们将探索（AIM 3）肠道微生物组的改变是否组成与炎症标记水平相关。职业发展部分奖项为PI提供了1）肠道微生物 - 免疫系统研究的详细培训； 2）进行独立研究调查所需的心理病理学研究方法饮食失调的生物标志物； 3）翻译科学设计，实施和管理; 4）负责任的研究。导师和顾问的专家团队将监督研究和培训目标，包括一位具有专业知识的现场主要导师在饮食失调和转化科学方面凭借肠道微生物组如何调节宿主免疫反应的专业知识，安德鲁·科（Andrew Koh）博士。博士科学顾问辛西娅·布里克（Cynthia Bulik）将提供有关将生物标志物与复杂联系起来的指导在精神病中看到的人类行为。另外两个科学顾问罗伯特博士 Haley（与神经免疫学有关的生物统计学专业知识）和Larry Borish博士（免疫功能和炎症途径的专业知识）完成指导团队。该提案中概述的研究和培训将提供至关重要的形式和体验培训以允许PI，董事会认证的内科医生，具有强大的研究背景胃肠道生理和免疫学，发展为独立的翻译医师科学家。