Common mechanisms of the microbiota-gut-brain axis in alcohol use disorder and depression: A genetically informed investigation

微生物群-肠-脑轴在酒精使用障碍和抑郁症中的常见机制：一项遗传信息调查

• 批准号: 10245127
• 负责人: Jarrod Martin Ellingson
• 金额: $ 18.06万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-27 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10245127
• 关键词: Address; Adult; Affect; Aftercare; Alcohol consumption; Alcohols; Biological; Biological Markers; Brain; Characteristics; Data; Depressed mood; Epigenetic Process; Funding; Gene Expression; Genes; Genetic; Genetic Risk; Goals; Health Care Costs; Healthcare; Heavy Drinking; Immune; Individual; Inflammation; Inflammatory; Inflammatory Response; Intervention; Investigation; Laboratories; Link; Longitudinal Studies; Major Depressive Disorder; Mental Depression; Mental Health; Mentorship; Modeling; Moods; National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; Nature; Pathway interactions; Principal Investigator; Process; Public Health; Relapse; Research; Research Training; Resources; Risk; Role; Sampling; Science; Symptoms; System; Training; Treatment outcome; Twin Multiple Birth; Twin Studies; alcohol abuse therapy; alcohol use disorder; base; brain behavior; cognitive control; cognitive function; cognitive process; cognitive task; comorbid depression; comorbidity; craving; cytokine; depressive symptoms; disability; effective therapy; genetic information; gut bacteria; gut microbiome; gut microbiota; heuristics; immune function; immunoregulation; inflammatory disease of the intestine; inflammatory marker; microbial; microbiota; microbiota-gut-brain axis; mindfulness; negative affect; patient oriented research; programs; psychiatric symptom; reduced alcohol use; skills

7. Project Summary Approximately one in three people seeking treatment for alcohol use disorder (AUD) also have major depressive disorder. These individuals use more health care resources but are twice as likely to relapse and have a greater level of disability after treatment. Consequently, the already high public health costs of AUD are likely exacerbated when other mental health problems co-occur. Further, there are no empirically supported treatments for AUD and comorbid depression, and applying an adjunct treatment for depression in comorbid cases is ineffective for reducing AUD relapse rates. This project aims to advance the science and treatment of AUD and co-occurring depression by investigating shared mechanisms across the microbiota-gut-brain axis, specifically involving digestive, immune, and cognitive processes. Disturbances to microbial species inhabiting the gut (i.e., microbiota) have been linked to alcohol use, mood, and cognitive control. Similarly, inflammatory markers and cognitive control are associated with AUD and depression. Extensive research has demonstrated that these systems are interrelated; disturbances to gut microbiota can increase circulating inflammatory markers, which then affect the brain and behavior. Thus, biological mechanisms across the microbiota-gut- brain axis may be targeted individually, or in tandem, to treat AUD and co-occurring depression. The overarching goal of this project is to identify promising treatment targets for AUD and co-occurring depression. Specifically, the research aims will investigate three components of the microbiota-gut-brain axis: (1) gut microbiota characteristics, (2) inflammatory cytokines, and (3) cognitive control. This project also aims to (4) understand how genetic factors are related to the effects of the microbiota-gut-brain axis, which has been greatly overlooked in this line of research. To achieve these research aims, this project uses data from an NIAAA-funded treatment study of AUD and an NIMH-funded study of cognitive control. Both studies have collected data across the microbiota-gut-brain axis, as well as data for examining the role of gene expression and general genetic risk. Analyses will investigate whether these mechanisms explain covariation among AUD and depressive symptoms. Further, exploratory analyses will investigate biological pathways, from gut to immune functioning, that underlie AUD and depression. The principal investigator, Dr. Ellingson, will also pursue training aims, which will broaden his skill set and enable him to (1) examine gut microbiota, (2) investigate inflammatory cytokines and other biomarkers, and (3) administer laboratory tasks of cognitive control. To guide his training and research, Dr. Ellingson has assembled a premiere mentorship team with expertise spanning the microbiota-gut-brain axis and in genetics. Thus, he will be supported as he develops skills and expertise necessary to launch a genetically informative, patient-oriented research program on biomarkers of AUD and co-occurring conditions.

7.项目摘要 大约三分之一寻求酒精使用障碍（AUD）治疗的人也有严重的 抑郁症这些人使用更多的卫生保健资源，但复发的可能性是其他人的两倍， 治疗后残疾程度更高。因此，澳元已经很高的公共卫生成本， 当其他心理健康问题同时发生时，可能会加剧。此外，没有经验支持 治疗AUD和共病抑郁症，并在共病抑郁症中应用辅助治疗。 例对降低AUD复发率无效。该项目旨在促进科学和治疗 通过研究微生物-肠道-大脑轴的共同机制， 特别是消化免疫和认知过程对栖息在 肠（即，微生物群）与酒精使用，情绪和认知控制有关。同样， 标记物和认知控制与AUD和抑郁症相关。广泛的研究表明， 这些系统是相互关联的;对肠道微生物群的干扰可以增加循环炎症 标记，然后影响大脑和行为。因此，微生物-肠道- 脑轴可以单独靶向，或串联靶向，以治疗AUD和并发的抑郁症。的 该项目的总体目标是确定AUD和共发抑郁症的有希望的治疗靶点。 具体而言，本研究的目的是研究微生物-肠道-脑轴的三个组成部分：（1）肠道 微生物群特征，（2）炎性细胞因子和（3）认知控制。该项目还旨在（4） 了解遗传因素如何与微生物群-肠道-大脑轴的影响有关， 在这方面的研究中被忽视了。为了实现这些研究目标，该项目使用了来自 NIAAA资助的AUD治疗研究和NIMH资助的认知控制研究。这两项研究都有 收集了微生物-肠道-大脑轴的数据，以及研究基因表达作用的数据， 和一般遗传风险。分析将调查这些机制是否解释AUD之间的协变 和抑郁症状。此外，探索性分析将研究从肠道到 免疫功能，这是AUD和抑郁症的基础。首席研究员艾林森博士还将 追求培训目标，这将扩大他的技能，使他能够（1）检查肠道微生物群，（2） 研究炎性细胞因子和其他生物标志物，和（3）管理认知的实验室任务 控制为了指导他的培训和研究，Ellingson博士组建了一个一流的导师团队， 在微生物-肠道-大脑轴和遗传学方面的专业知识。因此，他将得到支持，因为他的发展 技能和必要的专业知识，以启动一个遗传信息，以病人为导向的研究计划， AUD的生物标志物和共同发生的条件。