Bile reinfusion is associated with shifts in host-microbiota metabolic profiles following cholangiocarcinoma-associated microbiota transplantation

Abstract Cholangiocarcinoma (CCA) is a heterogeneous group of malignant tumours originating along the biliary tract. Previous studies have demonstrated that CCA is characterised by altered gut microbial composition and disrupted bile acid metabolism, both of which are critical determinants of host metabolic homeostasis. Although bile reinfusion (BR) has been proposed to improve surgical outcomes in CCA patients, its systemic metabolic effects and interaction with gut microbiota remain poorly understood. Here, we employed faecal microbiota transplantation (FMT) from CCA patients, with or without BR, into Wistar rats to investigate host-microbiota metabolic interactions using integrated 1 H NMR-based metabolomics and full-length 16S rRNA gene sequencing. Rats receiving CCA-derived microbiota displayed altered systemic metabolic phenotypes, characterised by lower levels of glucose, lactate, and succinate compared to normal microbiota recipients, whilst no significant differences in faecal metabolites were observed between these groups. Notably, BR was associated with shifts in gut microbial composition, marked by enrichment of Lactobacillaceae, altered intestinal fermentation metabolites (decreased short-chain fatty acids and increased succinate), and a convergence of peripheral plasma metabolite profiles towards those observed in healthy microbiota recipients. These findings reveal associations between bile reinfusion and shifts in microbial composition and systemic metabolic phenotypes, providing a basis for investigating microbiota-bile acid-host metabolic crosstalk and potential therapeutic implications for managing CCA-associated dysbiosis.