Dietary Guanidinoacetic Acid Supplementation Improves Growth Performance of Plateau Yaks Through Plasma Metabolome Modulation

This study aimed to investigate the effects of dietary guanidinoacetic acid (GAA) supplementation on yak physiology by evaluating growth performance, serum biochemical indices and plasm metabolomic profiles to elucidate the underlying regulatory mechanisms. Twenty-four male yaks (4-5 years; 249.38 ± 11.69 kg BW) were randomly allocated to three dietary treatments (<i>n</i> = 8): CON (basal diet), GAA1 (basal diet + 0.055% GAA), and GAA2 (basal diet + 0.11% GAA), with 55:45 of concentrate:roughage (DM basis). After a 10-day adaptation period, the feeding trial lasted 90 days. Body weights were measured on days 0 and 90 for growth performance evaluation, with blood samples collected on the final day for separation into serum and plasma to assess serum metabolic and antioxidant parameters and for plasma metabolomic profiling. The result showed that growth performance parameters displayed a positive trend, with average daily gain (ADG) showing marginal improvement (<i>p</i> = 0.072). Serum biochemical analysis revealed that dietary supplementation of GAA had no effect on serum biochemical parameters while tendency decreased GSH-Px activity (<i>p</i> = 0.087). Non-targeted metabolomics identified 39-121 differentially abundant metabolites in plasma across treatment groups. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of these metabolites revealed pathways such as tryptophan metabolism, glycerophospholipid metabolism, and arginine metabolism. Among the differentially abundant metabolites, N(omega)-Hydroxyarginine and tryptophan metabolites such as 5-hydroxytryptophan and serotonin were specifically highlighted. In conclusion, dietary supplementation of GAA in yaks has been confirmed to improve ADG, with a 0.11% supplementation level being more effective, and this may be associated with GAA enhancing amino acid metabolism, particularly arginine and tryptophan metabolism.