Rumen and colon-centered microbiota-liver interactions associated with bile acid-related metabolic regulation in...

Ruminant gastrointestinal microbiota are spatially heterogeneous, yet whether the rumen microbiota contributes to bile acid-related gut-liver associations beyond its local fermentative role remains unclear. Here, paired rumen, ileum, and colon microbiota were integrated with liver transcriptomic data, blood biochemical and tail fat-related phenotypes to determine which gastrointestinal sector microbiota play prioritized host interactions in a sheep model.

The rumen, ileum, and colon showed marked taxonomic and predicted functional divergence, indicating strong spatial restructuring along the digestive tract. Distinct patterns included rumen-enriched taxa, coordinated rumen-colon taxa, and taxa showing progressive shifts across compartments. Representative genera included Prevotella_7 and Butyrivibrio in rumen-enriched patterns, Anaerovibrio and Ruminococcus in coordinated rumen-colon patterns, and Fournierella and Treponema in colon-enriched patterns, whereas Olsenella and [Ruminococcus]_gauvreauii_group showed cross-compartment continuity. Pairwise correlation analyses revealed compartment-specific microbiota-host association profiles: both the rumen and colon formed major interfaces with hepatic bile acid-related genes, whereas the rumen showed broader associations with blood metabolic traits and tail fat deposition. The structure associated with serum total bile acids was most prominently associated with hepatic scavenger receptor class B member 1 (SCARB1), whereas the structures associated with serum triglycerides and tail fat mass were most prominently associated with hepatic phosphoenolpyruvate carboxykinase 1 (PCK1) and hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta (HADHB), respectively. Mediation analysis further provided statistical support for candidate intermediate associations involving hepatic genes between microbial variation and host phenotypes, with the strongest signals centered on serum total bile acids.

These findings indicate that the rumen is not merely a local fermentation chamber but may represent an important upstream microbial component associated with the bile acid-related gut-liver axis. Our results support consideration of an expanded, rumen-inclusive framework for investigating bile acid-related gut-liver associations in ruminants.