Lauren May¹, Alexander Khortus², Jasmohan S Bajaj³ and Jennifer T. Wolstenholme¹

Excessive alcohol consumption decreases gut microbiota diversity and is associated with microbial dysbiosis, defects in the intestinal mucosal barrier, and changes in immune responses. In a germ-free mouse model, our prior work has shown that the beneficial effects of a fecal microbiome transplant (FMT) from treated patients can be transmitted into mice to reduce ethanol intake. Importantly, live microbiota associated with butyrate production, but not their germ-free supernatants, were necessary to reduce drinking. These findings suggest that altering the microbiome in favor of short-chain fatty acid-producing bacteria may be a promising avenue for alleviating the symptoms associated with alcoholic liver disease and drinking. The goal of the current study is to determine what characteristics of FMT donors (bacterial diversity, engraftment efficiency) correlate with the greatest reduction in ethanol consumption. The endogenous gut microbiome was depleted in male and female C57BL/6 mice, followed by administration of one of three healthy human FMT samples and ethanol intake and preference was assessed. We found a robust sex difference in response to cross-species FMT. Two of the three donors significantly reduced ethanol intake and preference in female, but not male, mice. Ongoing metagenomic studies are evaluating microbiota chages during the course of engraftment and drinking to determine the specific characteristics of healthy FMT samples which may most contribute to lasting engraftment and reductions in ethanol drinking. These models of immunocompetent mice with cross-species FMT will provide a foundation for mechanistic studies on gut microbiome modulation as a way to influence ethanol consumption.

¹VCU-Alcohol Research Center and Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298

²Department of Medicine, University of Minnesota, Minneapolis, MN 55455

³Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298

Funding Support: NIAAA R21 AA031293