VCU news

By Olivia Trani

Researchers from Virginia Commonwealth University’s School of Medicine are conducting a clinical trial to better understand how transplantation of beneficial gut microbes could help people overcome their addiction to alcohol.

The study, called Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT), is the latest work led by Jasmohan Bajaj, M.D., a gastroenterologist and liver specialist who has been investigating the relationship between microbiomes, liver health and addiction-related diseases for years.

Our digestive system is home to a diverse ecosystem of bacteria and other microorganisms. Many of these microbes play key roles in maintaining our health and helping our bodies function, such as by digesting nutrients and warding off infection. Some research has shown that the microbes in our gut may also play a part regulating our brain and behavior. More than 100 million nerve cells line our gastrointestinal tract, allowing our gut and brain to communicate with each other through chemical signals. 

“There is an intense neuronal connection between the brain and the gut. If you change the gut environment significantly enough, you have the potential to not only impact the brain, but also in some ways our behavior,” said Bajaj, who is a professor in the Department of Internal Medicine’s Division of Gastroenterology, Hepatology and Nutrition in the VCU School of Medicine and a physician at the Richmond Veterans Affairs Medical Center.

Promising results

Bajaj has led research over the past few years to better understand how gut bacteria could be harnessed to help patients with alcohol addiction manage their drinking behavior.

“Excessive alcohol use has been a growing issue in the United States in recent decades, which only became worse as a result of COVID-19. We have young people in their 20s and 30s with end-stage liver disease who basically found themselves adrift during the pandemic,” Bajaj said. “Intestinal microbe transplantation could potentially be an additional tool to help patients overcome addiction.”

In an earlier, small-scale clinical trial, Bajaj worked with a collection of beneficial bacteria from a healthy person’s stool and transplanted them into 10 volunteers with severe alcohol use disorder and cirrhosis, an advanced stage of liver disease. Another 10 volunteers received a placebo treatment. In the study, published in Hepatology, nine of the volunteers from the bacteria transplant group experienced a reduction in alcohol craving and consumption, as well as improved cognition and quality of life, after 15 days. In contrast, only three of the placebo participants saw similar improvements. The bacterial transplant also translated into fewer hospitalizations from alcohol-related complications.

“Our first clinical trial was conducted on patients who have been drinking so much that their livers were completely damaged by cirrhosis,” Bajaj said. “I was stunned by the results because these are patients who, before receiving the microbe transplant, had not been able to stop drinking despite their best efforts and medications.”

To gain further evidence that microbial transplantation impacts drinking behaviors, Bajaj conducted a follow-up study in mouse models with Jennifer Wolstenholme, Ph.D., an assistant professor in the School of Medicine’s Department of Pharmacology and Toxicology, and other collaborators. The mice received a fecal sample collected from the trial participants either pre- or post-fecal transplant. Their findings, published in Nature Communications, mirrored the clinical trial’s outcomes. Mice treated with feces from patients who had received the healthy human microbial transplant exhibited significantly less alcohol preference and intake compared to the mice receiving pre-transplant feces from the same individuals.

“Our first clinical trial involved patients with various health conditions, like chronic pain, post-traumatic stress, depression and anxiety, all of which can affect how the brain and gut interact with each other,” Bajaj said. “Through mouse studies, we confirmed that gut microbes can play a part in inhibiting alcohol addiction.”

An expanded study

The new study, which is currently recruiting participants, will be a larger-scale clinical trial to examine the long-term clinical effectiveness of gut microbe transplants in patients with alcohol use disorder and cirrhosis. 

“The goal of our first clinical trial was to assess the safety of microbiota transplantation for patients,” Bajaj said. “This new study will allow us to follow participants with a more detailed alcohol behavioral focus to see whether this method has a prolonged positive impact in a larger group.”

Roughly 40 participants will be randomly assigned to receive capsules containing freeze-dried gut microbiota from healthy human donors twice during the study. A similar number of participants will receive placebo pills. This is being done in collaboration with Alexander Khoruts, M.D., a professor from the University of Minnesota Medical School. Through surveys and regular clinical check-ups, the researchers will assess how each participant’s alcohol use and cravings, health outcomes and gut microbiome change in the seven months following treatment. 

“People with alcohol use disorder are often dismissed by society as having a moral failing or weakness, but in reality it’s a medical disorder that requires medical treatment, just as you would treat a bone fracture,” Bajaj said. “Through this research, we hope to eventually give patients another possibility for treatment.”

The research is funded by the National Institute on Alcohol Abuse and Alcoholism, which is part of the National Institutes of Health. Individuals interested in participating or referring a potential participant in this trial can find more details online or contact Amy Bartels, via email or at (804) 828-3849.