Multi-omics reveal mechanisms of action of gut microbes and metabolites in infantile cholestatic hepatopathy

Background Infantile cholestatic hepatopathy (ICH) is a leading cause of pediatric liver transplantation. This study aimed to investigate the relationships between gut microbiota and metabolic profiles in ICH patients using integrated multi-omics approaches to elucidate underlying disease mechanisms. Methods Fecal samples from ICH infants and controls were analyzed. Gut microbiota composition was assessed via 16S rRNA gene sequencing, and microbial community differences were evaluated using Alpha/Beta diversity metrics and Linear Discriminant Analysis Effect Size (LEfSe). Concurrently, metabolomic profiles were generated and analyzed using multivariate statistics to identify differential metabolites, which were subsequently mapped to biochemical pathways. Spearman correlation analysis was performed to establish key microbe-metabolite associations. Results 16S rRNA sequencing yielded 2,189 Amplicon Sequence Variants. ICH samples showed significant alterations in microbial composition at multiple taxonomic levels and functional pathway enrichment. Metabolomic analysis identified 388 differential metabolites enriched in 53 pathways. Correlation analysis revealed 17 significant microbe-metabolite associations, with 9 key metabolites strongly linked to three bacterial genera: Veillonella, Actinomyces, and Bifidobacterium. Conclusions Integrative analysis identified specific correlations between gut microbiota dysbiosis and metabolic disturbances in ICH. The findings, highlighting 9 metabolites associated with three key bacterial genera, provide novel insights into ICH pathophysiology and potential targets for future preventive and therapeutic strategies.