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

Abstract

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.