Strain‐Specific Yeast Polysaccharides Enhance Growth, Antioxidant Capacity, Immune Response and Gut Microbiota Homeostasis in Red Tilapia Cultured Under Seawater Conditions

This study evaluated the antibacterial activity and functional effects of yeast polysaccharides derived from three Saccharomyces cerevisiae strains (L6, L9, and L10) on growth, immunity, and gut health of red tilapia cultured under seawater conditions. An in vitro antibacterial assay against V. parahaemolyticus and V. vulnificus was conducted, followed by a 16‐week feeding trial using six isonitrogen (crude protein: 370 ± 8 g kg −1 ) and iso‐energy (gross energy: 11.4 ± 0.2 MJ kg −1 ) diets: control, commercial β‐glucan, MOS, L6, L9, and L10, each at 1 g/kg. A total of 720 healthy fish (20.06 ± 0.06 g) were randomly assigned to 24 floating cages (1 × 1 × 1 m; four replicates per treatment). Results showed that all YPS exhibited antibacterial activity against Vibrio spp ., with L10 showing the strongest inhibition in vitro. Fish fed L10 also exhibited the highest weight gain rate (WG) and lowest feed conversion ratio (FCR) compared with the control group ( p < 0.05). Plasma biochemical indices indicated that the L10 group significantly increased total antioxidant capacity, and lysozyme while decreasing malondialdehyde ( p < 0.05). Meanwhile, the intestinal anti‐inflammatory cytokines were significantly upregulated, and the proinflammatory cytokines were significantly downregulated with the inclusion of yeast polysaccharide derived from the L10 strain ( p < 0.05). Furthermore, L10 also improved intestinal morphology and barrier integrity while modulating the microbiota toward beneficial taxa, characterized by increased Cetobacterium and reduced Photobacterium . Integrated transcriptomic and metabolomic analyses further revealed activation of immune‐, metabolism‐, and homeostasis‐related genes (e.g., PAPSS2 , rhbg , and CBS ), alongside the enrichment of amino acids and microbial metabolites (e.g., indole derivatives) associated with mucosal immune regulation. Overall, this study revealed that supplementation of 1 g/kg L10 yeast polysaccharide can promote growth, antioxidant capacity, immune homeostasis, and gut microbiota balance in red tilapia, highlighting the potential as next‐generation functional feed additives for sustainable marine aquaculture.