Immune Dysregulation in Eating Disorders (ID-ED)

饮食失调中的免疫失调 (ID-ED)

• 批准号: 10364647
• 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/10364647
• 关键词: Address; Adult; Ambulatory Care; Animal Model; Anorexia Nervosa; Award; Behavior; Behavior Disorders; Behavioral Symptoms; Binge Eating; Biological Markers; Biometry; 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; 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; Research Training; 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; 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)是一种以自我形象扭曲和精神障碍为特征的精神疾病 根据需要限制能量摄入，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 在患有AN的人中已经观察到，包括免疫学和 疾病期间的胃肠功能。然而，这些变化还没有相关的 观察到的认知和行为症状。这是K23指导的职业生涯 发展奖的提议是解决文献中这一差距的第一步。我们的建议 研究项目将评估免疫失调和肠道微生物组组成 在有健康对照的女性参与者中。在目标1中，我们描述了 通过评估基础细胞因子和固有细胞因子的产生来研究炎症的分子成分 容量。在目标2中，我们评估肠道微生物组的组成及其与 进食障碍症状。最后，我们将探索(目标3)肠道微生物群的变化 成分与炎症标志物水平相关。其中的职业发展部分 该奖项为PI提供了1)肠道微生物-免疫系统研究方面的详细培训；2) 开展独立研究调查所需的精神病理学研究方法 饮食失调中的生物标志物；3)翻译科学的设计、实施和 管理；以及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主要导师 在饮食失调和翻译科学方面，Carrie McAdams博士和现场的联合导师 拥有肠道微生物如何调节宿主免疫反应的专业知识，Andrew Koh博士。Dr。 Cynthia Bulik，一位科学顾问，将提供与复杂生物标记物相关的指导 精神疾病中的人类行为。另外两名科学顾问，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 (在免疫功能和炎症途径方面的专业知识)完成导师团队。 本提案中概述的研究和培训将提供重要的正式和经验 培训以允许PI，一名董事会认证的内科医生，具有强大的研究背景 胃肠生理学和免疫学，发展成为独立的翻译 医生兼科学家。