Gut microbiome and metabolome profiles in diverse etiologies of chronic liver disease

The gut-liver axis plays an important role in chronic liver disease (CLD), yet etiology-specific microbiome-metabolome profiles remain incompletely characterized. This exploratory multi-omics study investigated potential microbiome and metabolome differences across CLD etiologies. A total of 80 CLD patients were recruited, including 53 with hepatitis B virus (HBV) infection, 7 with alcohol-associated liver disease (ALD), 6 with drug-induced liver injury (DILI) and 14 with other unknown causes (OTH). Fecal samples were prospectively collected from all enrolled patients, followed by metagenomic sequencing and non-target metabolomic profiling. Concurrently, small intestinal mucosal biopsies were obtained from a 25-patient subset and subjected to metagenomic sequencing. Forty demographically matched healthy individuals were included as controls. Exploratory analyses suggested potential microbiome and metabolome differences among CLD etiologies. The ALD group showed potential differences in microbial composition and predicted functional pathways, although these findings should be interpreted cautiously given the small sample size. Metabolomic analysis identified etiology-associated metabolic features, and several metabolite panels showed preliminary discriminatory potential for differentiating disease groups within this cohort. Integrated microbiome and metabolome mapping suggested associations between microbial taxa and metabolic pathways related to host-microbe interactions along the gut-liver axis. This exploratory multi-omics study suggests potential etiology-associated microbiome and metabolome features in CLD. These preliminary findings provide candidate microbial and metabolic features for future mechanistic and stratification studies, but require validation in larger, well-balanced, independent cohorts before clinical application.