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 Verrucomicrobia, Actinobacteria, Faecalibacterium, Akkermansia, Intestinibacter, Phascolarctobacterium , and Ruminococcus , alongside increased Blautia and Coprococcus . These microbial shifts correlated with liver function indices, notably positive associations between Ruminococcus 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.