Multi-omics integration uncovers gut segment-specific gene-metabolite networks underlying growth retardation in piglets.

Weaning is a critical phase determining post-weaning growth and economic efficiency in pig production. To unravel gut segment-specific mechanisms underlying weaning weight variation, we performed integrated transcriptomic and metabolomic analyses of the mid-jejunum, ileum, and colon in high- (HWW) and low-weaning-weight (LWW) piglets. HWW piglets showed upregulated expression of amino acid transport genes (NOS2, ASS1, GPT2), alongside elevated levels of metabolites including glycochenodeoxycholic acid (GUDCA), deoxycholic acid (GDCA), methionine, and isoleucine. In the ileum, HWW piglets exhibited enrichment in ABC transporter and thyroid hormone pathways, with upregulated metabolites including betaine, cytidine, epigallocatechin, oxidized glutathione, cholylserine, and glutathione linked to enhanced immune homeostasis. In the colon, FUT2 and LYZ were key regulatory genes, and indole-3-carboxylic acid and enterolactone played critical roles in modulating colonic homeostasis. Taken together, our findings identify precise gene-metabolite networks driving intestinal functionality during weaning, offering targeted nutritional and genetic strategies to mitigate growth retardation in piglets.