FMT safe, shows promise in alcohol use disorder
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Fecal microbiota transplantation was associated with short-term reductions in alcohol craving and consumption in men with alcohol use disorder, according to research published in Hepatology.
Jasmohan S. Bajaj, MD, of the division of gastroenterology, hepatology and nutrition at Virginia Commonwealth University, and colleagues wrote that therapies that can encourage reduced alcohol use are critical tools against mortality and morbidities caused by alcohol use disorder (AUD) and alcohol-related cirrhosis.
“Other studies have demonstrated a potential role of microbiota in the addictive behavior,” they wrote. “We have shown that in patients with advanced cirrhosis who are not currently drinking, the altered gut-brain axis responds to fecal microbiota transplant.”
Researchers randomly assigned men with AUD-related cirrhosis with problem drinking (AUD identification test [IT]-10>8) to receive one placebo (n = 10) or FMT enema (n = 10) from a donor enriched in Lachnospiraceae and Ruminococcacea. The primary outcome of the study was safety at 6 months.
Investigators assessed alcohol craving, alcohol consumption, quality of life, cognition, serum IL-6, lipopolysaccharide-binding protein, plasma/stool short-chain fatty acids and stool microbiota at baseline and after 15 days.
Bajaj and colleagues found that a greater proportion of patients in the FMT group experienced significant reductions in alcohol cravings compared with the placebo group (90% vs. 30%; P = .02). They also had lower urinary ethylglucuronide/creatinine, improved cognition and psychosocial QOL.
Microbial diversity increased among the FMT group, with higher Ruminococcaceae and other short chain fatty acid producing taxa.
After 6 months, the placebo group had more patients with any severe adverse event (8 vs. 2; P = .02) and AUD-related severe adverse events (7 vs. 1; P = .02).
“We conclude in this phase 1 trial that FMT in men with cirrhosis is safe, associated with reduction in short-term craving and consumption with beneficial microbial change,” Bajaj and colleagues wrote. “The FMT assigned group also demonstrated lower AUD-related events over the follow-up, which need to be confirmed and extended in larger number of patients with AUD.”
Perspective
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Perturbations of the gut microbiome have been implicated in many diseases including those that fall on the brain-gut axis, such as substance addiction. Alcohol use disorder is one such example due to an emotional and physical dependence on alcohol. In a phase 1, placebo-controlled, randomized clinical trial, researchers demonstrate that a single enema with stool enriched in Lachnospiraceae and Ruminococcaceae alters the gut microbiome with greater populations of organisms that increase short chain fatty acid production and decrease inflammation. As a result, patients in the treatment group have decreased cravings for alcohol, lower consumption of alcohol and a better psychosocial quality of life.
This is a promising demonstration of the potential gut microbiome manipulation can have on diseases outside of Clostridioides difficile diarrhea. The patients were men who had alcoholic cirrhosis, had been drinking on average for 30 or more years and had failed multiple alcohol rehabilitation attempts. Although the sample size was small, a single dose led to differences in a group that had failed multiple therapies.
The primary endpoint of the study was the safety and efficacy of the enema. The enema was tolerated by all and there were only two serious adverse events for the 6-month duration of the trial in the FMT group, which was unrelated to the enema, vs. 8 in the placebo group.
Future studies should evaluate the number and dosing intervals required to maintain effects and non-cirrhotic populations who have not previously failed therapy.
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