Abstract
BACKGROUND: Alcohol use disorder (AUD) is linked to changes in the function and composition of the human gut microbiome (GM). The GM affects inflammation by producing anti-inflammatory molecules such as short-chain fatty acids (SCFA), in particular butyrate, which are linked to appetite regulation, a mechanism involved in alcohol craving. This study investigates changes in GM composition and functional capacity to produce SCFA during alcohol withdrawal and their link to inflammation and craving. METHODS: Sixty-three patients (mean age 48, SD = 12) with AUD were enrolled. We collected stool (n = 63) and blood (n = 48) during the first 48 h (timepoint A) of withdrawal therapy and between Days 10-14 (timepoint B). Microbiota were analyzed using shotgun metagenomics along with bacterial load determinations. TNF-α, IL-6, IL-8, and IL-10 were measured in plasma. RESULTS: Bacterial diversity (species richness, Shannon Index) did not change significantly throughout withdrawal, while overall bacterial load increased. Abundances of several taxa changed, and the overall community composition during withdrawal was approaching those of healthy controls; the potential to synthesize butyrate, a key SCFA, increased. However, it remained at lower levels compared with controls. Both diversity parameters correlated with cell concentrations and the butyrate pathway at baseline. The latter was negatively associated with IL-6 at baseline. IL-8 and IL-10 levels decreased significantly during withdrawal, as did craving, which was linked to abundance alterations of six species and IL-8. CONCLUSIONS: Alcohol withdrawal affected GM composition and increased concentration of the butyrate pathway along with overall bacterial load. Changes in bacterial composition and the butyrate production capacity demonstrate a shift toward healthier microbiota during withdrawal therapy. Changes in some species and IL-8 were linked to alcohol craving, replicating findings of previous studies. Our study adds new findings helping to understand the microbiome-gut-brain axis.