Liver alterations are not improved by inulin supplementation in alcohol use disorder patients during alcohol withdrawal: A pilot randomized, double-blind, placebo-controlled study

BACKGROUND: Emerging evidence highlights that targeting the gut microbiota could be an interesting approach to improve alcohol liver disease due to its important plasticity. This study aimed to evaluate the effects of inulin supplementation on liver parameters in alcohol use disorder (AUD) patients (whole sample) and in a subpopulation with early alcohol-associated liver disease (eALD). METHODS: Fifty AUD patients, hospitalized for a 3-week detoxification program, were enrolled in a randomized, double-blind, placebo-controlled study and assigned to prebiotic (inulin) versus placebo for 17 days. Liver damage, microbial translocation, inflammatory markers and 16S rDNA sequencing were measured at the beginning (T1) and at the end of the study (T2). FINDINGS: Compared to placebo, AST (β = 8.55, 95% CI [2.33:14.77]), ALT (β = 6.01, 95% CI [2.02:10.00]) and IL-18 (β = 113.86, 95% CI [23.02:204.71]) were statistically significantly higher in the inulin group in the whole sample at T2. In the eALD subgroup, inulin supplementation leads to specific changes in the gut microbiota, including an increase in Bifidobacterium and a decrease of Bacteroides. Despite those changes, AST (β = 14.63, 95% CI [0.91:28.35]) and ALT (β = 10.40, 95% CI [1.93:18.88]) at T2 were higher in the inulin group compared to placebo. Treatment was well tolerated without important adverse events or side effects. INTERPRETATION: This pilot study shows that 17 days of inulin supplementation versus placebo, even though it induces specific changes in the gut microbiota, did not alleviate liver damage in AUD patients. Further studies with a larger sample size and duration of supplementation with adequate monitoring of liver parameters are needed to confirm these results. Gut2Brain study: https://clinicaltrials.gov/ct2/show/NCT03803709 FUNDING: Fédération Wallonie-Bruxelles, FRS-FNRS, Fondation Saint-Luc.