Guanidinoacetic Acid and Cysteamine Hydrochloride Improve Beef Cattle Growth and Antioxidant Capacity via Fecal Microbiome and Serum Metabolome

Balancing muscle growth and antioxidant/anti-inflammatory homeostasis is a core requirement for modern beef production. This study investigated whether cysteamine hydrochloride (CSH) co-supplementation with guanidinoacetic acid (GAA) enhances growth and antioxidant status through fecal microbiome and serum metabolome modulation in Simmental beef cattle. A 60-day trial randomly assigned 45 10-month-old cattle to control (CON), GAA-supplemented, and GAA + CSH-supplemented groups (n = 15 per group). Growth performance was recorded throughout the trial. Fecal samples were collected for 16S rRNA sequencing, and serum samples for non-targeted metabolomics. Both GAA and GAA + CSH (GCSH) improved growth performance versus CON (p < 0.05), with no differences between supplemented groups. However, GCSH uniquely elevated antioxidant enzymes and reduced malondialdehyde (p < 0.05). GCSH treatment was associated with higher abundance of Adlercreutzia, Anaerofustis, and Monoglobus, alongside elevated indole-3-propionic acid and salicylsulfuric acid. In contrast, GAA reduced phenylacetyl-L-glutamine and indole-3-acetic acid. iCAMP analysis revealed that GCSH relieved homogenizing selection while enhancing heterogeneous selection, promoting beneficial taxa colonization. GAA primarily enhances nitrogen utilization, while CSH enriches beneficial microbiota and antioxidant metabolites. These findings suggest that GAA and CSH co-supplementation improves growth and antioxidant homeostasis through complementary mechanisms.