Characterizing the Microbiome-Gut-Brain Axis in Individuals with Alcohol Use Disorder

酒精使用障碍患者的微生物组-肠-脑轴特征

• 批准号: 10350459
• 负责人: Erica N Grodin
• 金额: $ 16.79万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10350459
• 关键词: 16S ribosomal RNA sequencing; Alcohols; Animal Model; Anxiety; Award; Bacteria; Base of the Brain; Big Data; Biological Markers; Blood specimen; Cells; Chronic; Clinical; Clinical assessments; Corpus striatum structure; Cues; Data; Development; Emotional; Executive Dysfunction; FABP2 gene; Goals; Growth; Homeostasis; Human; Individual; Intestinal permeability; Investigation; Link; Machine Learning; Mental Depression; Mentored Research Scientist Development Award; Mentors; Methods; Modeling; Neuraxis; Neurosciences; Participant; Pathogenesis; Phenotype; Play; Positioning Attribute; Process; Public Health; Recurrent disease; Research; Research Personnel; Role; Sampling; Scientist; Serum; Testing; Training; Work; addiction; alcohol craving; alcohol cue; alcohol response; alcohol use disorder; base; case control; chronic alcohol ingestion; cue reactivity; design; disorder control; dysbiosis; experience; gut bacteria; gut dysbiosis; gut microbiome; gut microbiota; gut-brain axis; incentive salience; intestinal homeostasis; microbial; microbiome analysis; microbiome composition; microbiota; microbiota-gut-brain axis; neural circuit; neuroimaging; non-alcoholic; pathogenic bacteria; phenomenological models; pre-clinical; problem drinker; random forest; relating to nervous system; therapy development

Project Summary/Abstract This K01 Mentored Research Scientist Development Award is designed to prepare the candidate to become an independent investigator in the emerging field of the gut microbiome in alcohol use disorder (AUD). AUD is a chronic relapsing disease with a major public health impact. While substantial research has been done to understand the neural circuitry underlying AUD, the role of the periphery and the connections between the periphery and the central nervous system have been understudied. One promising avenue of study is the gut microbiome and the microbiota-gut-brain axis, which have only recently been recognized as contributing to the pathogenesis of AUD. Despite the promise of the microbiota-gut-brain axis as an important contributor to AUD, there have been no comprehensive investigations of the microbiota-gut-brain axis in a single sample of individuals with AUD. Therefore, this proposal seeks to evaluate the relationship between gut dysbiosis, clinical phenomenology of AUD, and a brain-based biomarker in individuals with AUD and matched controls. The research objective of this K01 application is to characterize the microbiome-gut-brain axis across different levels of analysis. Specifically, 64 individuals with AUD and 64 matched healthy controls will provide a fecal sample to localize the effects of chronic alcohol use on the gut microbiome. Participants will also provide a blood sample to evaluate gut permeability through serum biomarkers. Participants will also complete an in- depth neuroscience-informed clinical assessment battery, which will allow for phenotyping individuals into the three domains of the Addiction Neuroclinical Assessment (ANA): incentive salience, negative emotionality, and executive dysfunction. Finally, participants with AUD will complete an alcohol cue-reactivity neuroimaging task to obtain a brain-based biomarker of AUD. The specific aims of the proposed project are: (1) to identify the gut microbiota discriminating individuals with AUD from controls; (2) to evaluate the relationship between the gut microbiome and AUD phenomenology; and (3) to test the relationship between gut microbiota and a brain- based biomarker for AUD. The successful completion of the above aims will provide the first data linking the microbiome-gut-brain axis to AUD in a clinical sample. This K01 award will position the candidate to be at the forefront of the AUD microbiome-gut-brain axis field. The training goals for Dr. Grodin are to gain expertise in (1) the gut-microbiome applied to AUD phenomenology, (2) quantitative methods in machine learning and big data, and (3) professional development as an independent scientist.

项目概要/摘要 K01 指导研究科学家发展奖旨在帮助候选人做好准备 成为酒精使用障碍（AUD）肠道微生物组这一新兴领域的独立研究者。 AUD 是一种慢性复发性疾病，对公共卫生产生重大影响。虽然已经进行了大量研究 这样做是为了了解 AUD 的神经回路、外周的作用以及之间的联系 外周神经系统和中枢神经系统已得到充分研究。一种有希望的研究途径是 肠道微生物群和微生物群-肠-脑轴，直到最近才被认为有助于 AUD的发病机制。尽管微生物群-肠-脑轴有望成为重要的贡献者 AUD，尚未对单个样本中的微生物群-肠-脑轴进行全面的研究 持有澳元的个人。因此，该提案旨在评估肠道菌群失调、临床 AUD 的现象学，以及 AUD 个体和匹配对照个体的基于大脑的生物标志物。这 该 K01 应用程序的研究目标是表征不同领域的微生物组-肠-脑轴 分析的层次。具体来说，64 名 AUD 个体和 64 名匹配的健康对照者将提供粪便 样本来定位长期饮酒对肠道微生物群的影响。参与者还将提供 血液样本通过血清生物标志物评估肠道通透性。参与者还将完成一个in- 深度神经科学知情的临床评估电池，这将允许对个体进行表型分析 成瘾神经临床评估（ANA）的三个领域：激励显着性、消极情绪和 执行功能障碍。最后，AUD 参与者将完成酒精提示反应性神经影像任务 获得基于大脑的 AUD 生物标志物。该项目的具体目标是：（1）确定肠道 微生物群将 AUD 患者与对照组区别开来； (2)评估肠道之间的关系 微生物组和 AUD 现象学； (3) 测试肠道微生物群与大脑之间的关系 基于 AUD 的生物标志物。上述目标的成功完成将提供第一个数据链接 临床样本中微生物组-肠-脑轴与 AUD 的关系。该 K01 奖项将使候选人处于 AUD 微生物组-肠-脑轴领域的前沿。格罗丁博士的培训目标是获得以下方面的专业知识 (1) 应用于 AUD 现象学的肠道微生物组，(2) 机器学习和大数据中的定量方法 数据，以及（3）作为独立科学家的专业发展。