Effects of Dietary Salvia sclarea L. Extract Supplementation on the Gut Microbiota, and Serum Metabolome in Lambs

Salvia sclarea L. extract contains various bioactive components such as flavonoids and fatty acids, exhibiting anti-inflammatory, antioxidant, and antibacterial properties. This study aimed to investigate the effects of Salvia sclarea L. extract on the gut microbiota and serum metabolome in lambs. Sixty 2-month-old Chinese Merino female lambs (body weight 20 ± 2 kg) were randomly assigned to five groups. The control (CK) group received the basal diet only, while the treatment groups received the basal diet supplemented with 0.04 mL/kg (CL1), 0.08 mL/kg (CL2), 0.12 mL/kg (CL3), and 0.16 mL/kg (CL4) of Salvia sclarea L. extract, respectively. The results showed that Firmicutes, Bacteroidetes, Spirochaetes, and Proteobacteria were identified as the dominant phyla across all groups (>90%). Compared with the CK group, CL1 and CL2 groups significantly reduced the relative abundance of Tenericutes (decreased by 38.2% and 32.9%, respectively, p < 0.05); the relative abundance of Patescibacteria in the CL1 group was significantly lower (decreased by 55.2%, p < 0.05). At the genus level, Ruminococcaceae constituted a substantial proportion, including Ruminococcaceae UCG-005, UCG-010, UCG-014, and NK4A214 group. STAMP analysis revealed that Klebsiella was significantly enriched in CL2, CL3, and CL4 groups compared to the CK group (p < 0.05). Correlation analysis between microbiota and immune indices showed that Christensenellaceae R-7 group was significantly negatively correlated with TNF-α (p < 0.05); Ruminococcaceae UCG-005 was significantly negatively correlated with IFN-γ (p < 0.05) and showed a negative correlation trend with immunoglobulins (IgA, IgG, IgM). Conversely, Ruminococcaceae UCG-014 was significantly positively correlated with IL-4 (p < 0.05) but showed a negative correlation trend with IgM. Untargeted metabolomics analysis identified 8, 18, 25, and 20 differential metabolites in CL1, CL2, CL3, and CL4 groups, respectively. Notably, 3-hydroxy-7-methoxyflavone and Gamma-Glu-Cys were significantly upregulated across all treatment groups. KEGG pathway enrichment analysis indicated that these differential metabolites were primarily involved in nucleotide metabolism, fatty acid biosynthesis, and oxidative stress-related pathways. Further Spearman correlation analysis revealed significant associations between gut microbiota and differential metabolites. Specifically, g_Klebsiella was significantly positively correlated with 3-Hydroxycapric acid and 3-hydroxy-7-methoxyflavone (p < 0.05). In conclusion, Salvia sclarea L. extract modulates host energy metabolism by regulating nucleotide metabolism and fatty acid biosynthesis, and enhances immune function by alleviating oxidative stress, through the remodeling of gut microbiota and serum metabolome.