Multiomics Analysis: Maternal Valine Intake during Protein Restriction Improves Fetal Intestinal Health in Pigs via IgA Homing

Protein restriction, while beneficial for maternal healthspan, poses risks to offspring development during lactation. This study investigated whether valine (Val) supplementation in maternal low-protein diets (LPDs) alleviates offspring developmental deficits via a gut-mammary axis. Maternal LPD impaired offspring growth, jejunal morphology, and barrier integrity while reducing levels of secretory immunoglobulin A (sIgA) and related immune mediators in both piglet jejunum and sow mammary gland. LPD suppressed CCL28-mediated sIgA homing to the mammary gland, which was restored by optimal Val supplementation (Val/Lys ratio: 0.88%). Val elevated serum valine metabolites and corrected LPD-induced depletion of beneficial genera in milk and the offspring gut, promoting microbial colonization. Thus, Val regulates sIgA immunity and microbial composition via the lactational axis to enhance the intestinal health of offspring under maternal protein restriction.