Examining the Role of the Gut-Brain Axis in Alcohol Use Disorder in Zebrafish

Abstract

14.5 million people struggle with Alcohol Use Disorder (AUD), characterized by uncontrolled drinking and withdrawal. Both chronic and acute alcohol use are known to disrupt the intestinal microbiome and are associated with mood disorders. The gut-brain axis is a bidirectional communication pathway between the brain and the intestines. Probiotic modulation has already been shown to alter brain chemistry in zebrafish. Recent research indicates the gut-brain axis is involved in the behavior modifications associated with AUD, however the mechanism by which it does so remains unknown. The objective of this study is to examine the impact that alcohol has on the gut-brain axis. We hypothesize that a reduced intestinal diversity will lead to heightened behavioral responses and alter biomarkers associated with chronic alcohol exposure. In order to examine this hypothesis, zebrafish (Danio rerio) were exposed to amoxicillin and erythromycin for fifteen days to clear their microbiome. Following treatment, fish were immersed in 0.50% ethanol for one hour and in escalating dosage up to 0.25% for two weeks to mimic acute and chronic alcohol exposure. Fish were recorded for 10 minutes following treatment to analyze behavioral patterns. Bacterial populations were significantly knocked down following treatment in both groups (n= 6, p < 0.05). Behavioral results from the acute ethanol treatment indicate fish exposed to ethanol displayed reduced vertical and horizontal transitions in both antibiotic and control groups, with more pronounced shifts in antibiotic-ethanol- treated group (n= 6). This reduction was not observed in the chronically treated fish, suggesting an adaptation effect. In order to further assess cognitive function, levels of NMDA Glut1 receptor mRNA were assessed, we observed no significant changes in receptor gene expression in the brains of zebrafish in the treatment groups relative to control groups. Collectively these results indicate that acute alcohol induced behavior correlates to changes in the microbiome, though this correlation is not observed in chronic alcohol exposure. Future studies are needed to better understand what role the gut brain axis plays in alcohol mediated-behavioral observations. Glen Raven Endowed Grant, Elon University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.