Integrative host-microbiome modeling uncovers the implication of oral-gut translocation in advanced cirrhosis.

Liver cirrhosis is associated with profound disruption of host-microbiome metabolic interactions. Using paired oral and fecal metagenomics combined with genome-scale metabolic modeling, we investigated how microbial translocation along the oral-gut axis influences microbial metabolism at different cirrhosis severities. Reactobiome-based functional profiling revealed progressive metabolic convergence between oral and gut microbiomes, quantified by a decrease in oral-gut metabolic distance. Translocation-associated microbial species enriched in patients with cirrhosis were predicted to have elevated capacities for ammonia and acetate production. Microbial-community and host metabolic modeling further suggested that these microbial metabolic shifts may influence host energy metabolism and redox balance across the liver, brain, and skeletal muscle. Together, these findings suggest a potential acetate-ammonia metabolic axis linking oral-gut microbial translocation with systemic metabolic stress in advanced cirrhosis.