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

项目摘要/摘要 K01指导研究科学家发展奖旨在帮助候选人准备 成为酒精使用障碍(AUD)肠道微生物群这一新兴领域的独立研究员。 AUD是一种慢性复发性疾病，对公共卫生有重大影响。虽然大量的研究已经在 以了解AUD背后的神经回路、外周的作用以及 对外周和中枢神经系统的研究还不够深入。一条很有希望的研究途径是 肠道微生物群和微生物区系-肠道-脑轴，直到最近才被认为对 AUD的发病机制。尽管微生物区系-肠道-脑轴有望成为 此外，还没有对单个样本中的微生物区系-肠道-脑轴进行全面的调查 患有澳门氏症的个人。因此，本建议旨在评估肠道生物失调与临床的关系。 AUD的现象学，以及AUD和匹配对照个体的基于大脑的生物标记物。这个 此K01应用程序的研究目标是表征不同类型的微生物群-肠道-脑轴 分析水平。具体来说，与澳大利亚大学硕士研究生学位论文匹配的健康对照将提供一份粪便 样本以确定长期饮酒对肠道微生物群的影响。参与者还将提供一个 取血标本，通过血清生物标志物评估肠道通透性。参与者还将完成一份In- 深度神经科学知情的临床评估单元，这将允许个人表型进入 成瘾神经临床评估(ANA)的三个领域：激励性显著、消极情绪性和 执行功能障碍。最后，患有AUD的参与者将完成酒精线索反应性神经成像任务 以获得AUD的脑生物标记物。拟议项目的具体目标是：(1)确定内脏 微生物区系区分AUD患者和对照组；(2)评估肠道之间的关系 微生物组和AUD现象学；以及(3)测试肠道微生物区系和大脑- 澳元的生物标记物。上述目标的成功完成将提供第一批数据，将 微生物组-肠道-脑轴到AUD的临床样本。这一K01奖项将使候选人在 AUD微生物-肠道-脑轴领域的前沿。格罗丁博士的培训目标是获得 (1)肠道微生物组在AUD现象学中的应用；(2)机器学习和BIG中的定量方法 数据，以及(3)作为独立科学家的职业发展。

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.