Study reveals new therapeutic approach for excessive alcohol consumption

In a significant finding, researchers at The Jackson Laboratory (JAX) and UConn Health have found that sodium valerate, a short-chain fatty acid produced by gut microbes, can dramatically reduce excessive alcohol drinking and blood ethanol concentrations in mice. The study, published June 17 in the Journal of the American Journal of Clinical Nutrition, reports MicrobiomeProvides promising insights into the gut-brain axis and presents a new therapeutic approach to excessive alcohol use.

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

The research team, led by Yanjiao Zhou, MD, PhD, associate professor of medicine at UConn Health, and Jason Bubier, PhD, senior research scientist at JAX, extensively examined the effects of short-chain fatty acid (SCFA) supplementation on alcohol consumption patterns in a mouse model. They administered three different SCFAs and found that sodium valerate decreased alcohol intake by 40% and blood ethanol levels by 53%. These results, along with significant molecular changes, suggest that sodium valerate may be a powerful new therapy to reduce alcohol drinking.

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

The study expands our understanding of the important connection between the gut microbiome and alcohol consumption. There is strong evidence that drinking alcohol significantly alters the microbiome in a way that accelerates the cycle of addiction through the gut-brain axis. Our findings provide a possible biological explanation for why this occurs and identify a potential treatment to reduce excessive alcohol consumption.”

Jason Bubier, Ph.D., Senior Research Scientist at JAX

Zhou, Bubier and their colleagues, including Suresh Bokolia, a postdoc in the Zhou lab, conducted further analyses comparing rats given sodium valerate with those given sodium chloride, commonly known as table salt, as a control. The data showed that sodium valerate not only reduced excessive alcohol drinking but also decreased anxiety-like or approach-to-avoidance behaviors compared with the control group. In addition, higher levels of gamma-aminobutyric acid (GABA), a neurotransmitter involved in neuropsychiatric and alcohol use disorders, were detected in the brain, feces and blood of the rats following sodium valerate supplementation.

Another important aspect of the study was to assess the effect 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 affects multiple signaling pathways in the brain, which may mediate its effects on alcohol consumption.

“The implications of our study are significant,” Zhou said. “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 abuse.”

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 excessive drinking and anxiety-like behaviors, offers a promising new avenue for the treatment of alcohol use disorders.