Study reveals potential therapeutic role of sodium valerate in reducing binge drinking

In a significant finding, researchers from The Jackson Laboratory (JAX) and UConn Health have discovered that sodium valerate, a short-chain fatty acid produced by gut microbes, can dramatically reduce binge drinking behavior and blood ethanol concentration in mice. The study, reported June 17 in Microbiome, offers promising insights into the gut-brain axis and presents a novel therapeutic approach for excessive alcohol use.

We are interested in physiological addiction genetics and genomics to identify new drug targets for treating addiction/overdose.

The research team, led by Yanjiao Zhou, M.D., Ph.D., associate professor of medicine at UConn Health, and Jason Bubier, Ph.D., senior research scientist at JAX, conducted a detailed investigation into the effects of short-chain fatty acid (SCFA) supplementation on alcohol consumption patterns in a mouse model. They administered three individual SCFAs and found that sodium valerate led to a 40% reduction in alcohol intake and a 53% decrease in blood ethanol levels. These results were accompanied by significant molecular changes that suggest sodium valerate could be a potent new therapy for reducing binge drinking.

Despite the widespread prevalence of alcohol use disorder, only three medications to date-disulfiram, naltrexone, and acamprosate-have been approved by FDA for treating patients. Most recently, the FDA approved naltrexone as an oral medication in 1994 and as an extended-release injectable in 2006.

“The study expands our understanding of the important relationship between the gut microbiome and alcohol consumption,” said Bubier. “There is strong evidence that binge drinking significantly alters the microbiome in ways that accelerate the cycle of addiction via the gut-brain axis. Our findings provide a possible biological explanation for why that occurs and identify a potential therapy for reducing excessive alcohol use.”

Zhou, Bubier and colleagues, including Suresh Bokoliya, a postdoc in the Zhou lab, conducted further analyses comparing mice administered sodium valerate with those given sodium chloride, commonly known as table salt, as a control. The data revealed that sodium valerate not only reduced binge drinking but also diminished anxiety-like or approach-avoidance behaviors compared to the control group. Furthermore, elevated levels of gamma-aminobutyric acid (GABA), a neurotransmitter implicated in neuropsychiatric and alcohol use disorders, were detected in the brain, stool, and blood of the mice following sodium valerate supplementation.

Another key aspect of the study involved assessing the impact of sodium valerate on brain function. Through RNA sequencing of the amygdala, a brain region associated with emotional regulation, the team identified significant changes in gene expression related to neuroinflammation, neurotransmission, mitochondrial regulation, and G protein-coupled receptor signaling. These findings suggest that sodium valerate influences multiple signaling pathways in the brain, which may mediate its effects on alcohol consumption.

"The implications of our study are significant," said Zhou. "By demonstrating how sodium valerate alters gene expression and neurotransmitter levels, we provide a multifaceted explanation for its potential as a treatment for excessive alcohol consumption."

This research underscores the critical role of the gut microbiome in addiction and highlights the therapeutic potential of targeting the gut-brain axis. Sodium valerate supplementation, with its ability to reduce binge drinking and anxiety-like behaviors, offers a promising new avenue for treating alcohol use disorders.

Reference:

Bokoliya, S.C., Russell, J., Dorsett, Y. et al. Short-chain fatty acid valerate reduces voluntary alcohol intake in male mice. Microbiome 12, 108 (2024). https://doi.org/10.1186/s40168-024-01829-6.