Integrated Multi-Omics Analysis Identifies Potential Associations of Unfermented and Fermented Astragalus Straw with Serum Antioxidant Status and Lipid Metabolism in Lambs

This study investigated the effects of fermented and unfermented Astragalus straw on serum antioxidant status, lipid metabolism, and hormone profiles in lambs and explored the underlying mechanisms using 16S rRNA sequencing and untargeted metabolomics. Twenty-seven weaned lambs were randomly assigned to three groups: a control group fed a basal total mixed ration (CON), an unfermented Astragalus straw supplementation group (AM_S), and a fermented Astragalus straw supplementation group (FAM_S). The experiment consisted of a 15-day adaptation period followed by a 90-day feeding period. At the end of the trial, growth performance was evaluated and serum samples were collected. Six lambs from each group were randomly selected and euthanized for the collection of rumen fluid and liver tissues for omics analyses. Compared with the CON group, both the AM_S and FAM_S groups showed significantly improved growth performance (p < 0.05). Furthermore, glutathione peroxidase (GSH-Px) activity and Adipose triglyceride lipase (ATGL) levels were significantly increased, whereas Low-density lipoprotein cholesterol (LDL) levels, resistin, and insulin (INS) concentrations were significantly decreased in the supplemented groups (p < 0.05). Microbiota analysis revealed that g_norank_f_F082 and f_F082 were enriched in the CON group, g_UCG-009 and f_Butyricicoccaceae were enriched in the AM_S group, and f_norank_o_Clostridia_vadinBB60_group and o_Clostridia_vadinBB60_group were enriched in the FAM_S group (p < 0.05). Untargeted metabolomics analysis showed that differential metabolites in the AM_S group were enriched in the α-linolenic acid metabolism and vitamin digestion and absorption pathways in both serum and liver samples, with gluconolactone and 9-oxononanoic acid identified as key associated metabolites. Interestingly, metabolites associated with the neuroactive ligand–receptor interaction pathway showed distinct enrichment patterns between serum and liver samples in the FAM_S group, with adenosine and tryptamine identified as key associated metabolites. Correlation analysis further revealed significant associations among serum antioxidant indicators, lipid metabolism-related parameters, hormone levels, differential metabolites, and rumen microbial genera. In conclusion, supplementation with unfermented or fermented Astragalus straw improved antioxidant capacity (GSH-Px) and modulated lipid metabolism-related parameters (ATGL, LDL-C, resistin, and INS) in lambs. These changes were accompanied by alterations in rumen microbiota and serum metabolites, supporting the potential application of Astragalus straw as a functional feed ingredient for ruminants.