High-Altitude Adaptation Mechanisms in Sheep Elucidated via Digestive Tract Metabolomics

High-altitude adaptation in Bayanbulak sheep may modulate digestive tract functions. This study aims to investigate the differences in digestive tract metabolites between Bayanbulak sheep at high altitude (2,400-4,400 m) and Turpan black sheep at low altitude (-154 m). Untargeted metabolomics technology was used to analyze metabolites in ruminal fluid, small intestinal contents, and feces. Serum biochemical parameters were measured, and morphological sections of skin tissue were observed. The results show:(1) Bayanbulak sheep exhibited significantly greater levels including total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), interferon-gamma (IFN-gamma), interleukin-2 (IL-2), total cholesterol, glucose, and triglyceride levels compared to Turpan black sheep (p < 0.05);(2) Epidermal thickening was observed in Bayanbulak sheep under high-altitude conditions;(3) Significant upregulation of metabolites including spermidine, 5'-adenylic acid (AMP), oleic acid (OA), and nicotine occurred in Bayanbulak sheep, accompanied by enhanced activity in glutathione metabolism, AMP-activated protein kinase (AMPK) signaling pathway, purine metabolism, and thermogenesis pathways;(4) Co-detected metabolites - vanillin, pinacidil, and 4-hydroxychalcone (4-HC) - exhibited significant differential abundance across rumen, small intestine, and feces in Bayanbulak sheep, with concurrent upregulation of associated metabolic pathways;(5) In the rumen of Bayanbulak sheep, differentially expressed genes CPT1B (carnitine palmitoyltransferase 1B), CPT1C (carnitine palmitoyltransferase 1C), and CASTOR2 (cytosolic arginine sensor for mTORC1 subunit 2) were significantly upregulated (p<0.05), collectively enriched in the AMPK signaling pathway and mTOR signaling pathway. Conversely, the small intestinal gene TM4SF18 (transmembrane L six family member 18) was significantly downregulated (p<0.01), co-enriched in the ferroptosis pathway.