Highlights d Gut alterations are related to impaired sociability in alcohol use disorder patients d Human-to-mice microbiota transplantation reproduces metabolic and behavioral disorders d Microbial ethanol production is linked to reduced b-hydroxybutyrate (BHB) synthesis d In mice and humans, BHB level is associated with depression and social impairments

Background & aims: Chronic alcohol consumption can cause malnutrition that may contribute to alcoholinduced organ injury and psychological disorders. We evaluated the link between nutrient intake, especially dietary fibers (DF) and different parameters reflecting mental health and well being, namely anxiety, depression, alcohol craving, sociability, fatigue and intestinal comfort in alcohol use disorder (AUD) patients. Methods: Cross-sectional data from 50 AUD patients, hospitalized for a 3-week detoxification program were used. Three 24-h recalls allowed to calculate dietary habits and nutrient intakes, that was also assessed in healthy subjects (HS). Diet quality was measured using the NOVA score. Psychological factors and intestinal discomfort were evaluated using validated self-administered questionnaires. Results: Energy intake (excluding alcoholic beverage), total fat, monounsaturated and polyunsaturated fatty acids, protein and DF intakes were lower in AUD subjects compared to HS. Ninety percent of patients had a DF intake below the recommendation. AUD patients consumed more than twice as much ultra-processed food than HS. Fructan intake was negatively associated with anxiety (p ¼ 0.04) adjusted for main confounders. Total DF, insoluble, soluble DF and galacto-oligosaccharide intakes were associated with higher sociability score. Soluble DF intake was associated with better satisfaction of bowel function (p ¼ 0.02) and a lower intestinal discomfort (p ¼ 0.04). Conclusions: This study reveals that insufficient DF intake is part of AUD-related malnutrition syndrome, and is associated with higher anxiety, lower sociability score and intestinal discomfort. Our results suggest that an adequate intake of DF might be beneficial for recovery from AUD. Trial registration: NCT03803709, https://clinicaltrials.gov/ct2/show/NCT03803709.

Alcohol use disorder (AUD) is a chronic relapsing disease associated with malnutrition, metabolic disturbances, and gut microbiota alterations that are correlated with the severity of psychological symptoms. This study aims at supplementing AUD patients with prebiotic fiber during alcohol withdrawal, in order to modulate the gut microbiota composition and to evaluate its effect on gastrointestinal tolerance, metabolism, and patient’s behavior. A randomized, double-blind, placebo-controlled study included 50 AUD patients assigned to inulin versus maltodextrin daily supplementation for 17 days. Biological measurements (fecal microbial 16S rDNA sequencing, serum biology), dietary intake, validated psychological questionnaires, and gastrointestinal tolerance assessment were performed before and after the intervention. Inulin significantly decreased the richness and evenness and induced changes of 8 genera (q < 0.1) including Bifidobacterium and Bacteroides . Prebiotic had minor effects on gastrointestinal symptoms and nutritional intakes compared to placebo. All patients showed an improvement in depression, anxiety, and craving scores during alcohol withdrawal regardless of the intervention group. Interestingly, only patients treated with inulin significantly improved the sociability score and had an increased serum level of brain-derived neurotrophic factor. This pilot study shows that inulin is well tolerated and modulates the gut microbiota and the social behavior in AUD patients, without further improving other psychological and biological parameters as compared to placebo. Gut2Brain study, clinicaltrial.gov: NCT03803709, https://clinicaltrials.gov/ct2/show/NCT03803709

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