Multi-omics Insights Into the Effect of Feeding Yeast Culture on the Liver Metabolism and Immunity of Plectropomus leopardus.

Yeast culture (YC) is widely applied as a functional feed additive, yet the mechanisms by which it regulates hepatic health, metabolism, and immune capacity in teleosts remain unclear. Here, juvenile Plectropomus leopardus were fed diets supplemented with 2.0% (YC2.0) or 8.0% YC (YC8.0) for 60 days, followed by hepatic histophysiological assessment, liver transcriptomic/metabolomic profiling, and an in vitro hepatocyte challenge with nervous necrosis virus (NNV). YC2.0 pincreased lipid droplet accumulation, improved antioxidant status, and lower aspartate aminotransferase(AST)/alanine aminotransferase (ALT)/alkaline phosphatase (ALP) and MDA in the liver than the control (Con) and YC8.0 groups. RNA-seq identified 915 hepatic differentially expressed genes (DEGs): YC2.0-specific genes were enriched in steroid hormone biosynthesis, bile secretion, and rhythmic regulation, whereas YC8.0-upregulated clusters were enriched in NOD-like receptor and JAK-STAT signaling, hematopoietic cell lineage, and apoptosis, with elevated immune- and apoptosis-related markers (nlrp1, mcub, myc, map1lc3b, and gadd45β/γ). Metabolomics identified 680 differential metabolites across the three groups, showing that YC2.0 predominantly enhanced purine/nucleotide and glycerophospholipid metabolism, while YC8.0 shifted toward amino acid-centered pathways (arginine biosynthesis, histidine metabolism, and FoxO signaling). Multiomics integration revealed positive correlations of L-aspartic acid (L-Asp) and glutamic acid (Glu) with inflammatory DEGs, and of glycerophosphoethanolamine (Geptn) with apoptosis-related DEGs. In vitro, YC pretreatment alleviated NNV-induced cytopathic effects (CPEs) in hepatocytes, suppressed viral mRNA accumulation, and reduced the mRNA levels of inflammatory cytokines (il1β, ifng, il6, il12a, il16, and tnfsf14) and immune pathway related DEGs. Collectively, these results characterize dose-dependent effects of YC on hepatic physiology and immune regulation, supporting its application as a functional aquafeed supplement.