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.

项目总结/摘要 这个K 01指导研究科学家发展奖旨在准备候选人， 成为酒精使用障碍（AUD）肠道微生物组新兴领域的独立研究者。 AUD是一种慢性复发性疾病，对公共卫生有重大影响。虽然大量的研究已经 这样做是为了了解AUD背后的神经回路，外围的作用和之间的连接， 外周和中枢神经系统尚未得到充分研究。一个有希望的研究途径是 肠道微生物组和微生物群-肠道-脑轴，直到最近才被认为有助于 AUD的发病机制。尽管微生物-肠-脑轴有望成为 AUD，没有对单一样本中的微生物-肠-脑轴进行全面研究。 个人AUD因此，本建议旨在评估肠道生态失调、临床和病理学之间的关系。 AUD的现象学，以及AUD个体和匹配对照中的基于脑的生物标志物。的 该K 01应用程序的研究目标是表征不同的微生物组-肠道-脑轴 分析水平。具体而言，64名患有AUD的个体和64名匹配的健康对照将提供粪便样本。 样本来定位长期饮酒对肠道微生物组的影响。参与者还将提供一个 血液样品以通过血清生物标志物评估肠道渗透性。参与者还将完成一个- 深度神经科学知情的临床评估电池，这将允许表型个体进入 成瘾神经临床评估（ANA）的三个领域：激励显着性，消极情绪， 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的脑生物标志物。本课题的具体目标是：（1）确定肠道 微生物群区分AUD个体与对照;（2）评估肠道之间的关系 微生物组和AUD现象学;以及（3）测试肠道微生物群和脑- 基于生物标志物的AUD。上述目标的成功完成将提供第一个数据， 微生物组-肠-脑轴与临床样品中AUD的关系。此K 01奖将定位候选人在 AUD微生物组-肠道-脑轴领域的前沿。Grodin博士的培训目标是获得以下方面的专业知识： (1)肠道微生物组应用于AUD现象学，（2）机器学习中的定量方法和大规模 数据，（3）专业发展作为一个独立的科学家。