Transcriptome, Proteome, and Metabolome Features in Diarrhea Challenge of Preweaning Piglets via Multi-Omics Integration Analyses

Preweaning piglet diarrhea not only compromises animal health but also causes significant economic losses to the swine industry; however, the underlying molecular mechanisms remain poorly understood. Here, we use a preweaning piglet model to systematically explore the underlying risk features of pre-weaning diarrhea risk through multi-omics integration analysis. We identified thousands of differentially expressed genes, proteins, and metabolites. Key findings include: (1) activation of the complement cascade but downregulation of complement receptors; (2) increased chemokine production with reduced receptor expression; (3) overexpression of mitochondrial ribosomal proteins (MRPs) and NADH: ubiquinone oxidoreductase (NDUF), suggesting mitochondrial dysfunction; (4) aberrant activation of neuroactive ligand–receptor pathways; and (5) accumulation of undigested polypeptides in the jejunum due to reduced peptidase activity and amino acid transporter expression, indicating disrupted protein digestion and absorption. These findings provide critical insights and a valuable resource for addressing the underlying mechanisms of preweaning disease challenges in newborns.