Immune Dysregulation in Eating Disorders (ID-ED)

饮食失调中的免疫失调 (ID-ED)

• 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
• 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

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， 相对于需求的能量摄入限制，导致体重显著降低，以及 经常导致严重的医疗并发症。因此，许多生理变化 已经观察到AN患者中的差异，包括免疫学和 疾病期间的胃肠功能。然而，这些变化尚未与 在AN期间观察到的认知和行为症状。K23职业生涯 发展奖提案是解决文献中这一差距的第一步。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AN的女性和健康对照参与者中。在目标1中，我们描述了 通过评估基础和先天性细胞因子的产生， 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，我们将探索（目标3）肠道微生物组的改变是否 组成与炎症标志物水平相关。职业发展部分， 该奖项为PI提供以下方面的详细培训：1）肠道微生物组-免疫系统研究; 2） 精神病理学研究方法进行独立的研究调查 饮食失调中的生物标志物; 3）转化科学设计，实施和 管理;（4）负责任的研究行为。由导师和顾问组成的专家团队 将监督研究和培训目标，包括一名具有专业知识的现场初级导师 在饮食失调和转化科学，博士凯莉麦克亚当斯，和现场共同导师 拥有肠道微生物组如何调节宿主免疫反应的专业知识，Andrew Koh博士。博士 科学顾问Cynthia Bulik将提供有关生物标志物与复杂 精神疾病中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 （免疫功能和炎症通路的专业知识）完成导师团队。 本提案中概述的研究和培训将提供至关重要的正式和经验 培训，让PI，一个董事会认证的内科医生与强大的研究背景， 胃肠道生理学和免疫学，发展成为一个独立的翻译 物理学家兼科学家