Office of Research & Development
Office of Research & Development
Dr. Jasmohan Baja is a gastroenterologist and researcher with VA and Virginia Commonwealth University. (Photo by Jason Miller)
September 10, 2020
By Tristan Horrom
VA Research Communications
"This study is a proof of concept that the way to the brain in through the gut."
Fecal transplant therapy is safe and can reduce alcohol craving and use in patients with alcohol use disorder, found a VA study. The preliminary study by Central Virginia Veterans Healthcare System and Virginia Commonwealth University researchers showed that fecal microbiota transplant could be safe and potentially effective towards reducing alcohol misuse, pending further research.
“This study is a proof of concept that the way to the brain in through the gut,” said Dr. Jasmohan Bajaj, first author on the study. “This, if confirmed in larger studies, may have implications for alcohol misuse and potentially other substance abuse disorders that are based on addictive behavior and are very common in our Veterans.”
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The results appeared in the journal Hepatology on Aug. 4, 2020.
Cirrhosis, scarring of the liver, can result from heavy drinking. Continued alcohol misuse after cirrhosis can hasten the disease’s progression. Previous research has shown that alcohol use disorder is associated with changes in the bacteria in the gut. These changes in gut microbiota—the collection of microorganisms within the body—can make cirrhosis worse.
Alcohol use disorder, with or without cirrhosis, is also linked to major changes in the gut-brain axis, the communication between the central nervous system and the gastrointestinal tract. Research has shown that gut microbiota can influence brain signaling, affecting cognition. Some research has even suggested that the bacterial make-up of the digestive system is involved in addictive behavior and could be linked to alcohol intake.
To explore this connection, the research team performed a randomized clinical trial of fecal microbiota transplant versus placebo on 20 patients at the Hunter Holmes VA Medical Center. In the transplant, processed fecal matter from a donor is enriched with beneficial bacteria and introduced into the patients. The patients in the study were then monitored for six months. All patients had cirrhosis and alcohol use disorder, and had failed or were unwilling to participate in usual therapies. In addition, many also had depression and PTSD. These co-occurring conditions made the patients unable to stop drinking even though they had already damaged their livers, explains Bajaj.
Fifteen days into the study, nine transplant patients had reduced alcohol cravings, compared with only three in the placebo group. This was accompanied by lower urinary Etg/creatinine levels, a measure of actual alcohol intake.
This is the first human study to test fecal microbiota transplant to potentially reduce alcohol addiction, according to Bajaj. Prior animal studies have shown a linkage between the microbiota and alcohol intake.
The transplant group also had reduced levels of markers associated with systemic inflammation. These positive changes were not seen in the placebo group.
Tests showed that fecal transplant led to increased microbial diversity in the gut. Microbe diversity did not change in the placebo group. Patients who received the transplant had a greater abundance of beneficial bacteria and products such as short-chain fatty acids, which can affect the brain. Some of these bacteria are usually decreased in alcohol-related cirrhosis and liver disease. More of this type of bacteria is associated with protection from alcohol-induced intestinal and liver injury.
The transplant group also showed signs of improved mental function, as well as improvement in psychosocial but not physical quality of life. This likely indicates that both brain function and the patients’ assessment of their cognitive abilities had improved, says Bajaj.
The fecal transplant group also improved on several measures at six months. They showed a trend toward abstinence from alcohol, although this result was not statistically significant. Most in the placebo group showed evidence of continued alcohol misuse.
Furthermore, the results show that fecal transplant is safe. Only two of the transplant group had serious adverse events after the procedure, compared with eight in the placebo group. A safety board concluded that neither of the adverse events in the transplant group was related to the procedure. Seven of the eight adverse events in the placebo group were tied to alcohol use disorder, which varied from alcohol relapse, alcohol withdrawal, motor vehicle accidents and falls requiring urgent medical attention.
The researchers call the results “encouraging.” Microbial manipulation could potentially lead to improvements in cirrhosis and alcohol use disorder, they say.
The linkage between decrease cravings and bacteria is also interesting, according to the researchers. It could be evidence of how the microbiota regulates the gut-brain axis. But they caution that larger studies are needed to explore this connection.
On the whole, say the researchers, the study shows that fecal microbiota transplant has real potential as a safe and effective treatment for future study in reducing alcohol craving and consumption in patients with cirrhosis.
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