Colonization Modulates Murine Ethanol Consumption and Behavioral Responses Through Elevation of Serum Prostaglandin E and Impact on the Striatal Dopamine System.

Unlabelled: is a commensal yeast that is a common component of the gastrointestinal (GI) microbiome of humans. has been shown to bloom in the GI tract of individuals with alcohol use disorder (AUD) and can promote and increase the severity of alcoholic liver disease (ALD). However, the effects of blooms on the host in the context of AUD or AUD-related phenotypes, such as ethanol preference, have been unstudied. In this work, we report a reduction in ethanol consumption and preference in mice colonized with . colonized mice exhibited elevated levels of serum PGE and reduced ethanol preference was reversed by injection with antagonists of PGE receptors. Further, injection of mice with a PGE derivative decreased their ethanol preference. These results show that PGE acting on its receptors EP1 and EP2 drives reduced ethanol preference in colonized mice. We also showed altered transcription of dopamine receptors in the dorsal striatum of colonized mice and more rapid acquisition of ethanol conditioned taste aversion, suggesting alterations to reinforcement or aversion learning. Finally, -colonized mice were more susceptible to ethanol-induced motor coordination impairment showing significant alterations to the behavioral effects of ethanol. This study identifies a member of the fungal microbiome that alters ethanol preference and demonstrates a role for PGE signaling in these phenotypes.

Importance: is a commensal yeast that is found in the gut of most individuals. has been shown to contribute to alcoholic liver disease. Outside of this, the impact of intestinal fungi on alcohol-use disorder (AUD) had been unstudied. As AUD is a complex disorder characterized by high relapse rates, and there are only 3 FDA-approved therapies for the maintenance of abstinence, it is important to study novel AUD contributors to find new therapeutic targets. Here we show that an intestinal fungus, , can alter mammalian ethanol consumption through an immune modulator, prostaglandin E . The results highlight novel contributors to AUD-related phenotypes and further implicate the gut-brain axis in AUD. Future studies could lead to new therapeutic avenues for the treatment of AUD.