Lactobacillus rhamnosus: A Novel Probiotic Therapy for treating Alcohol Use Disorder

鼠李糖乳杆菌：一种治疗酒精使用障碍的新型益生菌疗法

• 批准号: 10191836
• 负责人: Vatsalya Vatsalya
• 金额: $ 14.08万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-10 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10191836
• 关键词: Abstinence; Adverse effects; Adverse event; Albumins; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Animals; Attenuated; Award; Behavior Therapy; Behavioral; Bilirubin; Biochemical Markers; Biochemistry; Biological Assay; Biological Markers; Blood; Blood Circulation; Brain; Chronic; Clinical; Clinical Research; Complex; Data; Diagnosis; Dietary Fiber; Disease; Disulfiram; Double-Blind Method; Endotoxemia; Enrollment; Equipment and supply inventories; FDA approved; Faculty; Fermentation; Frequencies; Functional disorder; Goals; Grant; Health; Healthcare; Heavy Drinking; Hepatitis; Human; Inflammation; Inflammatory; Intervention; Intestinal permeability; Knowledge; Lactobacillus casei rhamnosus; Lead; Lipopolysaccharides; Liver; Liver diseases; Mediating; Medical; Mentors; Mentorship; Methodology; Naltrexone; National Institute on Alcohol Abuse and Alcoholism; Neurotransmitters; Outcome; Pathway interactions; Patient Outcomes Assessments; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Pilot Projects; Placebos; Positioning Attribute; Probiotics; Prognostic Marker; Psychological reinforcement; Public Health; Publications; Quality of life; Randomized; Regulation; Relapse; Reporting; Research; Research Personnel; Research Project Grants; Resources; Rewards; Role; Severities; Structure; Symptoms; Testing; Therapeutic; Training; United States; Universities; Withdrawal; Woman; Work; Writing; alcohol use disorder; base; bench to bedside; candidate marker; chronic alcohol ingestion; comorbidity; craving; design; drinking; effective therapy; efficacy testing; efficacy validation; eligible participant; experience; gut microbiome; gut microbiota; gut-brain axis; improved; liver development; liver inflammation; liver injury; men; metabolomics; microbiome alteration; neurobehavioral; neuroinflammation; new therapeutic target; novel; organ injury; preventable death; probiotic therapy; programs; response; restoration; skills; success; symptomatic improvement; tenure track; therapeutic target; treatment adherence; treatment comparison; treatment trial

This application is a proposal for a mentored clinical research award (K23) that will enable Dr. Vatsalya Vatsalya to continue to develop his skills in clinical research; specifically, identifying new therapeutic targets for the treatment of patients with alcohol use disorder (AUD) and concomitant moderate alcohol associated hepatitis (AH). AUD represents one of the leading causes of preventable deaths in the United States and efforts are in progress to identify new interventions. Emerging animal and human research suggest that Lactobacillus rhamnosus GG (LGG), a probiotic, is involved in the restoration of a normal gut microbiome, attenuating gut dysfunction and lowering endotoxemia and inflammation. Dr. Vatsalya’s overall goal is to complete mentored research and transition to independent research. He also plans to successfully obtain a tenure-track faculty position that will allow him to fully establish his own independent research program. Dr. Vatsalya’s training goals are to: (1) broaden his conceptual knowledge in researching the neuropharmacological mechanisms in AUD; (2) enhance his experience with human studies in the field of AUD and alcohol associated liver disease (ALD); (3) improve his methodological skills in order to conduct effective large-scale trials; and (4) improve his grant- and publication-writing skills. These training goals will be achieved through: (a) the resources available at the University of Louisville; (b) the high quality of mentorship provided by his mentor and the mentor committee; (c) focused training and clinical experiences; and (d) the proposed research project. During the award period, Dr. Vatsalya’s goals are to: (1) complete the K23 research and develop preliminary data to conduct a larger bedside-to-bench study using the results and skills obtained during the K23 grant; and (2) apply for an NIAAA investigator-initiated (R01) grant based on the preliminary outcomes. Alcohol consumption is associated with altered microbiome and gut dysfunction, increased gut permeability, systemic endotoxemia (gut-derived bacterial products in the circulation), and proinflammatory activity. The gut dysfunction observed with heavy drinking has also been associated with the development of liver injury and inflammation observed in ALD. The research component of Dr. Vatsalya’s application will investigate if LGG can restore normal gut function, reduce gut permeability and proinflammatory activity, thereby improving the symptomology of concomitant AUD and ALD. The proposed research project extends Dr. Vatsalya’s previous work on the pharmacological treatment of AUD and on the role of LGG in mediating the gut-brain axis that could be expanded to identifying new interventional-mechanistic targets in AUD.

本申请是指导临床研究奖（K23）的提案，将使Vatsalya博士 Vatsalya继续发展他在临床研究方面的技能;特别是，确定新的治疗靶点， 治疗酒精使用障碍（AUD）伴中度酒精相关的患者 肝炎（AH）。澳元是美国可预防死亡的主要原因之一， 正在努力确定新的干预措施。新兴的动物和人类研究表明， 鼠李糖乳杆菌GG（LGG）是一种益生菌，参与恢复正常的肠道微生物组， 减轻肠道功能障碍并降低内毒素血症和炎症。Vatsalya博士的总体目标是 完成指导研究并过渡到独立研究。他还计划成功获得一个 终身教职，这将使他能够完全建立自己的独立研究计划。博士 Vatsalya的培训目标是：（1）扩大他的研究概念知识， AUD的神经药理学机制;（2）增强他在AUD领域的人体研究经验 和酒精相关性肝病（ALD）;（3）提高他的方法技能，以进行有效的 大规模的试验;（4）提高他的赠款和出版物的写作技巧。这些培训目标将实现 通过：（a）路易斯维尔大学的可用资源;（B）提供的高质量指导 （c）重点训练及临床经验;及（d）建议的 研究项目。在获奖期间，Vatsalya博士的目标是：（1）完成K23研究， 利用获得的结果和技能开发初步数据，以进行更大规模的床旁到实验台研究 在K23赠款期间;以及（2）根据初步的申请申请NIAAA仲裁员发起的（R 01）赠款 结果。饮酒与微生物组改变和肠道功能障碍有关， 渗透性、全身性内毒素血症（循环中的肠源性细菌产物）和促炎性 活动在大量饮酒中观察到的肠道功能障碍也与以下疾病的发生有关： 在ALD中观察到肝损伤和炎症。Vatsalya博士申请的研究部分将 研究LGG是否可以恢复正常的肠道功能，降低肠道通透性和促炎活性， 从而改善伴随的AUD和ALD的病理学。该研究项目扩展到 博士Vatsalya先前关于AUD的药物治疗以及LGG在介导AUD中的作用的工作， 肠脑轴，可以扩展到确定新的干预机制的目标，在AUD。