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）是一种精神疾病，其特征是自我形象扭曲和相对于需求限制能量摄入，导致体重显着降低，以及经常导致严重的医疗并发症。因此，许多生理变化已观察到 AN 患者的差异，包括免疫学和疾病期间胃肠功能。然而，这些变化尚未关联 AN 期间观察到的认知和行为症状。 K23 指导职业发展奖提案是解决文献中这一空白的第一步。我们提出的研究项目将评估免疫失调和肠道微生物组成患有 AN 的女性和健康的对照参与者。在目标 1 中，我们描述了通过评估基础和先天细胞因子的产生来确定炎症的分子成分容量。在目标 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，我们将探讨（目标 3）肠道微生物组是否发生改变成分与炎症标志物水平相关。本部分的职业发展部分该奖项为 PI 提供 1) 肠道微生物组-免疫系统研究方面的详细培训； 2）进行独立研究调查所需的精神病理学研究方法饮食失调的生物标志物； 3）转化科学设计、实施和管理; 4) 负责任地进行研究。由导师和顾问组成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饮食失调和转化科学领域的凯莉·麦克亚当斯博士和现场共同导师 Andrew Koh 博士在肠道微生物组如何调节宿主免疫反应方面拥有丰富的专业知识。博士。科学顾问辛西娅·布利克 (Cynthia Bulik) 将提供有关生物标志物与复杂的相关性的指导在精神疾病中看到的人类行为。另外两名科学顾问罗伯特博士 Haley（神经免疫学相关生物统计学专业知识）和 Larry Borish 博士（免疫功能和炎症途径方面的专业知识）完善了指导团队。本提案中概述的研究和培训将提供重要的形式和经验 PI 是一位经过委员会认证的内科医生，具有丰富的研究背景胃肠生理学和免疫学，发展成为独立的转化学医生科学家。