Shared signatures of alcohol-associated dysbiosis in humans and non-human primates

Alcohol use disorder (AUD) is a chronic brain disease with limited therapeutic options. Increasing evidence suggests that the gut microbiome contributes to AUD via the microbiome-gut-brain axis. Here, we conducted a cross-species investigation of gut microbiota alterations in patients with clinically diagnosed AUD and in non-human primates (NHPs) subjected to long-term alcohol (ethanol) self-administration, using metagenomic sequencing. Both cohorts showed reduced microbial diversity and conserved dysbiosis, with consistent depletion of <i>Verrucomicrobia, Actinobacteria, Faecalibacterium, Akkermansia, Intestinibacter, Phascolarctobacterium</i>, and <i>Ruminococcus</i>, alongside increased <i>Blautia</i> and <i>Coprococcus</i>. These microbial shifts correlated with liver function indices, notably positive associations between <i>Ruminococcus</i> and bilirubin levels in both species, suggesting a potential role in liver injury. Functional analyses revealed conserved microbial adaptations, including upregulated DNA repair pathways, fermentative energy metabolism, and downregulated glutamate/glutamine biosynthesis. Together, these results identify evolutionarily conserved microbial and metabolic alterations linking alcohol consumption, gut dysbiosis, and hepatic dysfunction. Our cross-species evidence highlights the gut microbiome as a potential biomarker and therapeutic target for AUD.