Abstract

The mandarin fish ( Siniperca chuatsi ) is an economically important species in China, yet its innate predatory behavior poses significant challenges for adaptation to artificial feed. Understanding the intestinal adaptive mechanisms during the early stages of dietary transition is crucial for developing effective artificial feeds. In this study, 1500 juvenile fish were stocked in each of six net cages (3 m × 2 m × 2 m). Three cages were assigned as the control group, continuously fed live prey (L), and three as the treatment group, switched to an artificial diet (A) after a two-week acclimation. Intestinal samples were collected at 1 week (A1) and 3 weeks (A2) post-transition for histomorphological, transcriptomic, and metabolomic analyses. Histological assessment revealed significant enhancements in intestinal architecture in the diet-fed group, including increased villus height, muscularis thickness, and goblet cell number ( P  < 0.05). Transcriptomic profiling indicated significant upregulation of genes associated with digestion ( try1, pla2 ), lipid metabolism ( fads2, fabp4a, dhcr7 ), and immune function ( traf4a, il20ra, lamp2 ) ( P  < 0.05). KEGG enrichment analysis of differentially expressed genes identified 10 pathways consistently enriched at both time points, encompassing lipid metabolism (e.g., Steroid biosynthesis, PPAR signaling) and immune-related processes (e.g., Lysosome, mTOR signaling). Metabolomic analysis further demonstrated a time-dependent immune and metabolic shift: the A1 group showed elevated levels of 2′-acetylamino-p-phenylenediamine and leukotriene B4 ( P  < 0.05), suggesting initial immune activation, while the A2 group exhibited a rise in oxidative stress markers (9(S)-HODE and 12,13-DiHOME) ( P  < 0.05). Corresponding metabolic pathway analysis highlighted upregulation of PPAR signaling and taurine metabolism in A1, and enhanced activity of ABC transporters, linoleic acid metabolism, and glutathione metabolism in A2. Multi-omics i