Multi-omics reveals the molecular mechanisms of rapid growth in distant hybrid fish

Distant hybridization usually results in heterosis. In previous studies, we obtained an improved fish (WR-II, 2n = 100) with rapid growth through distant hybridization. To investigate the molecular mechanisms underlying the rapid growth of WR-II, the intestinal structure, microbiome and metabolome of the gut and the transcriptome of muscle were compared between WR-II and its parents (WCC and RCC, 2n = 100). The results revealed that WR-II had more intestinal folds, and the height, width and goblet cell density of the intestinal folds were greater than those of its parents. The absolute abundances of the probiotics Ralstonia and Salinivibrio were significantly greater in WR-II than in the parents (p < 0.05), and the probiotic Cupriavidus was found in only WR-II. A total of 481 and 718 differentially abundant metabolites (DMs) were identified in WR-II vs. WCC and WR-II vs. RCC, respectively. These DMs were enriched mainly in pathways related to metabolism, protein synthesis and development, such as fumaric acid, sphingosine, betaine and 5 '-adenylic acid (AMP). A total of 5680 and 11,795 differentially expressed genes (DEGs) were identified in WR-II vs. WCC and WR-II vs. RCC, respectively. These DEGs were enriched mainly in pathways related to protein synthesis and substance metabolism. Growth-related genes such as irs1, irs2, foxo1, igf1r, and akt were upregulated in WR-II. Multi-omics analysis revealed that Salinivibrio can promote the level of AMP, which then regulates the expression of irs1 and foxo1, thus promoting the growth of WR-II. This study revealed the mechanism of rapid growth of WR-II from the probiotics, metabolites and genes, which provides evidence for the molecular mechanism of heterosis.