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

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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.