Bile Acids Modulate Hepatic Glycolipid Metabolism via the Microbiota-Gut-Liver Axis in Lambs.

Abstract

Background: Bile acids are essential molecules that facilitate lipid emulsification and function as signaling molecules mediating host-microbiota interactions. They shape the gut microbial structure and function, playing a critical role in metabolic regulation via the gut-liver axis.

Objectives: This study aimed to investigate the effects of exogenous bile acids, primarily hyocholic acid (HCA), on the microbiota-gut-liver metabolism in male Tan-lambs fed a high-grain diet.

Method: Thirty six-month-old male Tan lambs (Ovis aries) were randomly allocated into either a control (CON) group or an HCA-supplemented group (n = 15 per group). The trial lasted 84 days, including a 14-day adaptation period. On day 70, six lambs from each group were randomly selected for slaughter. Rumen and ileal contents were collected for microbial profiling via 16S rRNA sequencing, and liver tissue samples were harvested for transcriptomic and metabolomic analyses.

Results: The HCA intervention significant altered the composition and structure of ruminal and ileal bacteria. Notable increases were observed in Turicibacter (linear discriminant analysis (LDA) score = 2.48; P < 0.05) and Muribaculaceae (LDA score = 3.75; P < 0.05) in the rumen, and Eubacterium fissicatena group (LDA score = 2.50; P < 0.05) in the ileum. Key hepatic genes and metabolites targeted by HCA were identified, including ENPP3, RFK, Ifi203, LIPG, CYP1A1, CYP4A11, nordeoxycholic acid (log-fold change = 6.30, P < 0.005), α-muricholic acid (log-fold change = 5.60, P < 0.001), β-muricholic acid (log-fold change = 5.60, P < 0.001).

Conclusions: Exogenous bile acids regulate the microbiota-gut-liver axis, influencing hepatic glycolipid metabolism in sheep. Specifically, nordeoxycholic acid, demonstrates potential as a dietary intervention to promote metabolic homeostasis in ruminants. These findings highlight the potential of HCA and norDCA as functional feed additives or prebiotic agents for improving metabolic health in ruminants and potentially other species.