Gut microbiome dynamics and alcohol use outcomes during naltrexone treatment: a 12 week follow-up study

Alcohol use disorder (AUD) is a heterogeneous condition. Growing evidence highlights the role of the gut-brain axis in alcohol-related behaviors; however, longitudinal changes in the gut microbiome during pharmacological treatment for AUD remain poorly understood. In this 12-week study, we investigated gut microbiome composition and functional profiles in individuals with AUD undergoing naltrexone treatment. Seventy-two patients meeting DSM-5 criteria for AUD were enrolled. Stool samples were collected at baseline, week 4, and week 12 and analyzed using high-throughput 16 S rRNA gene followed by bioinformatic analyses. Of the 72 enrolled participants, 32 and 23 completed stool sampling at weeks 4 and 12, respectively. Despite significant improvements in drinking behavior over the treatment period, no significant changes in α- or β-diversity were observed, and no distinct clustering of gut microbial communities emerged across timepoints. Notably, the relative abundance of the Eubacterium hallii group increased from baseline and remained elevated through week 12. Several specific bacterial taxa were significantly associated with drinking outcomes and craving severity, particularly abstinence days (or inversely drinking days). At week 12, β-diversity, but not α-diversity, differed significantly between abstinence and non-abstinence groups. Functional enrichment analyses indicated that naltrexone treatment predicted functional reorganization of the gut microbiome based on 16 S inference, characterized by enhanced xenobiotic degradation and remodeling of cofactor-dependent antioxidant metabolism. Naltrexone treatment had limited effects on overall gut microbiota structure. In contrast, AUD patients who achieved sustained abstinence exhibited a distinct gut microbiota profile, suggesting that microbiome functional dynamics may contribute to AUD recovery and reflect treatment response to naltrexone. The absence of a placebo or untreated AUD control group precludes conclusions about the independent effects of naltrexone on gut microbiome changes.