Multi-omics integration uncovers adaptive responses of stomach and pyloric ceca to artificial feed in mandarin fish...

The mandarin fish, as an obligate piscivore, is highly dependent on live bait, which restricts its intensive aquaculture. Although domestication has enabled it to partially accept formulated diets, the tissue-specific molecular adaptation mechanisms of its digestive tract to artificial feed remain unclear. In this study, we conducted an integrated analysis of mandarin fish fed with live bait or artificial diet for three weeks, combining growth performance evaluation, gastric histology, and paired transcriptomic and metabolomic analyses of the stomach and pyloric ceca. AD feeding significantly improved growth performance, while histological examination revealed marked hyperplasia of the gastric mucosa and disorganized fold structures. Transcriptomic analysis identified 5065 and 3381 differentially expressed genes in the stomach and pyloric ceca, respectively. In the stomach, the artificial diet induced a glutathione-dependent antioxidant response, accompanied by glycolytic reprogramming and coordinated upregulation of genes in the extracellular matrix (ECM)-receptor interaction signaling pathway, including those encoding collagen, laminin, and integrin. In the pyloric ceca, the tricarboxylic acid (TCA) cycle and oxidative phosphorylation were broadly suppressed, whereas glycosaminoglycan degradation and lysosomal pathways were activated. Metabolomic analysis showed that gastric metabolites were enriched in vascular and inflammatory mediator pathways, while metabolites in the pyloric ceca were enriched in peroxisome proliferator-activated receptor (PPAR) signaling, sphingolipid signaling, and steroid hormone biosynthesis pathways. Following artificial diet feeding, integrated multi-omics analysis of the stomach revealed significant enrichment of pathways such as phospholipase D signaling, sphingolipid signaling, and arachidonic acid metabolism, accompanied by the accumulation of key metabolites including sphingosine-1-phosphate, 20-hydroxyeicosatetraenoic acid, and cellobiose. Integrated analysis of the pyloric ceca identified significantly altered pathways, including sphingolipid metabolism, alpha-linolenic acid metabolism, and glutathione metabolism, along with elevated levels of sphingosine-1-phosphate, sphingosine galactoside, and 9-hydroxy-12-oxo-10,15-octadecadienoic acid, as well as decreased glutathionylspermidine. These findings systematically unveil the tissue-specific molecular adaptation characteristics of the mandarin fish digestive tract in response to artificial feed, providing an important basis for understanding the molecular mechanisms of dietary adaptation in carnivorous fish and for optimizing artificial feed formulations.