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: 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
• 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

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.

该申请是一个指导临床研究奖（K23）的提案，将使Vatsalya博士

项目成果

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
• 作者: McClain,CraigJ;Kirpich,Irina;Song,Ming;Vatsalya,Vatsalya
• 通讯作者: Vatsalya,Vatsalya

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

• DOI: 10.4236/jbbs.2023.134005
• 发表时间: 2023-04
• 期刊: Journal of behavioral and brain science
• 作者: Naskar A;Jayanty D;Head K;Khanna GL;Vatsalya V;Banerjee A
• 通讯作者: Banerjee A

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.