Effects of extensive protein hydrolysate in supporting intestinal barrier function in vitro

Extensively hydrolyzed proteins (eHP) derived from cow's milk improve intestinal barrier function and cell viability in a fetal organoid-derived model of premature human intestine. This is the first study to assess the functional and transcriptomic impact of eHP on primary intestinal epithelial cells derived from fetal organoids, a highly relevant model for preterm gut physiology. It demonstrates that eHP-unlike intact proteins or free amino acids-can mitigate inflammation-induced permeability and modulate pathways involved in epithelial proliferation and repair (e.g., NOTCH, WNT, E2F, G2M checkpoint). These findings highlight the potential of eHP as a nutritional strategy to enhance gut integrity and limit inflammatory damage in preterm infants, who are at high risk of intestinal complications such as NEC. This study paves the way for further mechanistic and clinical research on how peptide-based formulas might support immature gut function and reduce extraintestinal risks.