A Randomized Clinical Trial of Fecal Microbiota Transplant for Alcohol Use Disorder.

BACKGROUND & AIMS Alcohol use disorder (AUD) is associated with microbial alterations that worsen with cirrhosis. Fecal microbiota transplant (FMT) could be a promising approach. APPROACH & RESULTS In this phase 1, double-blind, randomized clinical trial, AUD-related cirrhosis patients with problem drinking (AUDIT-10>8) were randomized 1:1 into receiving one placebo or FMT enema from a donor enriched in Lachnospiraceae and Ruminococcaceae. 6-month safety was the primary outcome. Alcohol craving questionnaire, alcohol consumption (urinary ethylglucuronide/creatinine, Etg), quality of life (QOL), cognition, serum IL-6 and lipopolysaccharide-binding protein (LBP), plasma/stool short-chain fatty acids (SCFA) and stool microbiota were tested at baseline and day 15. A 6-month follow-up with serious adverse events (SAE) analysis was performed. 20 patients with AUD-related cirrhosis [65±6.4 years, all men, MELD 8.9±2.7] with similar demographics, cirrhosis and AUD severity were included. Craving reduced significantly in 90% of FMT versus 30% in placebo at day15(p=0.02) with lower urinary Etg (p=0.03), improved cognition and psychosocial QOL. There was reduction in serum IL-6 and LBP and increased butyrate/isobutyrate compared to baseline in FMT but not placebo. Microbial diversity increased with higher Ruminococcaceae and other SCFA producing taxa post-FMT but not placebo, which were linked with SCFA levels. At 6 months, patients with any SAEs (8 vs 2, p=0.02), AUD-related SAEs (7 vs 1, p=0.02) and SAEs/patient [median(IQR),1.5(1.25) vs 0(0.25) in FMT,p=0.02] were higher in placebo versus FMT. CONCLUSIONS This phase 1 trial shows that FMT is safe and associated with short-term reduction in alcohol craving and consumption with favorable microbial changes versus placebo in patients with alcohol-related cirrhosis with alcohol misuse. There was also a reduction in AUD-related events over 6 months in patients assigned to FMT.