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

基本信息

批准号：
10620258
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
项目类别：
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/10620258
关键词：
Abstinence Adverse effects Adverse event Albumins Alcohol consumption Alcoholic Hepatitis Alcoholic Liver Diseases Alcoholic beverage heavy drinker Alcohols Animal Model Animals Award Behavior Therapy Behavioral Bilirubin Biochemical Markers Biochemistry Biological Assay Biological Markers Blood Brain Chronic Circulation Clinical Clinical Research Complex Data Diagnosis Dietary Fiber Disease Disulfiram Dopamine 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 Inflammatory Response Intervention Intestinal permeability Knowledge Lactobacillus casei rhamnosus Lipopolysaccharides Liver Liver diseases Measures 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 Property Psychological reinforcement Public Health Publications Quality of life Randomized Regulation Relapse Reporting Research Research Personnel Research Project Grants Resources Rewards Role Serotonin Severities Structure Symptoms Testing Therapeutic Training Tryptophan United States Universities Volatile Fatty Acids Withdrawal Woman Work Writing alcohol use disorder bench to bedside candidate marker chronic alcohol ingestion comorbidity craving design drinking effective therapy efficacy testing efficacy validation eligible participant experience gamma-Aminobutyric Acid 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

项目摘要

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.

该申请是修订临床研究奖（K23）的提案，该奖项将使Vatsalya博士启用 Vatsalya继续发展他的临床研究技能；具体而言，确定新的治疗靶标饮酒障碍患者（AUD）和伴随现代酒精相关的患者的治疗肝炎（AH）。 AUD代表了美国可预防死亡的主要原因之一和正在努力确定新的干预措施。新兴动物和人类研究表明乳酸乳杆菌GG（LGG），一种益生菌，参与正常肠道微生物组的恢复，衰减肠道功能障碍并降低内肌血症和炎症。 Vatsalya博士的总体目标是完整的指导研究并过渡到独立研究。他还计划成功获得终身教师职位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）扩大他在研究中的概念知识 AUD中的神经药物机制；（2）增强他在AUD领域人类研究的经验和酒精相关的肝病（ALD）；（3）提高他的方法学技能以进行有效大规模试验；（4）提高他的赠款和出版撰写技巧。这些培训目标将得到实现通过：（a）路易斯维尔大学可用的资源；（b）提供的高品质提供通过他的心理和心理委员会；（c）重点培训和临床经验；（d）提议研究项目。在颁奖期间，Vatsalya博士的目标是：（1）完成K23研究和使用获得的结果和技能来开发初步数据，以进行更大的床头至基础研究在K23赠款期间；（2）申请基于初步的NIAAA研究者发起的（R01）赠款结果。饮酒与微生物组和肠道功能障碍的改变有关，肠道增加渗透性，全身性内毒素血症（循环中肠道衍生的细菌产物）和促炎性活动。大量饮酒观察到的肠道功能障碍也与在ALD中观察到的肝损伤和炎症。 Vatsalya博士申请的研究部分将调查LGG是否可以恢复正常的肠道功能，降低肠道渗透性和促炎活性，从而改善了伴随AUD和ALD的症状。拟议的研究项目扩展了 Vatsalya博士以前关于AUD的药物治疗以及LGG在调解aud的作用的工作可以扩展的肠脑轴以确定AUD中的新介入机械目标。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Association of Hypomagnesemia and Liver Injury, Role of Gut-Barrier Dysfunction and Inflammation: Efficacy of Abstinence, and 2-Week Medical Management in Alcohol Use Disorder Patients.

DOI：
10.3390/ijms231911332
发表时间：
2022-09-26
期刊：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
影响因子：
5.6
作者：
Winrich, Evan J.;Gala, Khushboo S.;Rajhans, Abhas;Rios-Perez, Christian D.;Royer, Amor J.;Zamani, Zarlakhta;Parthasarathy, Ranganathan;Marsano-Obando, Luis S.;Barve, Ashutosh J.;Schwandt, Melanie L.;Vatsalya, Vatsalya
通讯作者：
Vatsalya, Vatsalya

Illustration of Gut-Thyroid Axis in Alcohol Use Disorder: Interplay of Gut Dysfunction, Pro-Inflammatory Responses, and Thyroid Function.

DOI：
10.3390/cells11193100
发表时间：
2022-10-01
期刊：
Cells
影响因子：
6
作者：
Sagaram M;Royer AJ;Hu H;Rajhans A;Parthasarathy R;Krishnasamy SS;Mokshagundam SP;Kong M;Schwandt ML;Parajuli D;Cave MC;Vatsalya V
通讯作者：
Vatsalya V

Keratin 18-M65: A biomarker for early-stage alcohol-associated liver disease.

角蛋白 18-M65：早期酒精相关肝病的生物标志物。

DOI：
10.1111/acer.15117
发表时间：
2023
期刊：
Alcohol, clinical & experimental research
影响因子：
0
作者：
McClain,CraigJ;Kirpich,Irina;Song,Ming;Vatsalya,Vatsalya
通讯作者：
Vatsalya,Vatsalya

Elevated stearoyl-CoA desaturase 1 activity is associated with alcohol-associated liver disease.

DOI：
10.1016/j.alcohol.2022.04.001
发表时间：
2022-08
期刊：
ALCOHOL
影响因子：
2.3
作者：
Klepp, T. D.;Sloan, M. E.;Soundararajan, Soundarya;Ramsden, C. E.;Cinar, R.;Schwandt, M. L.;Diazgranados, N.;Vatsalya, V.;Ramchandani, V. A.
通讯作者：
Ramchandani, V. A.

Diagnostic Prospectives with Tau Protein and Imaging Techniques to Detect Development of Chronic Traumatic Encephalopathy.