Multi-omics reveals that rumen fluid transfer affects the immune function of Xizang sheep by regulating enterohepatic metabolic homeostasis.

The gut microbiota plays a crucial role in immune regulation and metabolic homeostasis in ruminants; however, the systemic effects of rumen fluid transfer (RFT) on the gut-liver axis remain unclear. In this study, Xizang sheep were used as the animal model to investigate the effects of RFT using multi-omics approaches, including transcriptomics, metabolomics, and 16S rRNA sequencing. The results showed that RFT was associated with changes in immune- and metabolism-related genes (e.g., TLR4, NOD2, PPARA, and ABCG2) and alterations in several key metabolites, including tryptophan-related compounds, amino acids, and bile acid-associated metabolites. RFT was also associated with shifts in gut microbial composition, as reflected by changes in the relative abundance of genera such as Prevotella, Ruminococcus, and Lactobacillus. Integrated multi-omics analysis indicated coordinated associations among gut microbiota, metabolites, and host gene expression along the gut-liver axis. These findings indicate that RFT may be linked to immune and metabolic regulation in Xizang sheep, providing a systems-level framework for understanding microbiota-host interactions.