Protective role of seleno-amino acid against IBD via ferroptosis inhibition in enteral nutrition therapy

The interplay between intestinal barrier degradation and trace element insufficiency worsens inflammatory bowel disease (IBD). Selenium (se) is essential for glutathione peroxidase 4 (GPX4) synthesis, which protects against intestinal epithelial cell injury in IBD. However, malnutrition and malabsorption limit the availability of dietary selenium. This study investigated the protective effects of naturally occurring seleno-amino acids on the intestinal barrier in an IBD animal model by promoting GPX4 synthesis. L-se-methylselenocystine (seMc) supplementation reversed decreased GPX4 expression levels, alleviated glutathione depletion and scavenged reactive oxygen species in vitro. In vivo, enteral nutrition combined with seMc protected the intestinal barrier and alleviated IBD-related symptoms by inhibiting ferroptosis and reversing lipid peroxidation in epithelial cells while reducing immune cell infiltration. Our findings suggest that seleno-amino acid-based nutritional formulations may provide a basis for nutritional support to alleviate complex cycles between intestinal barrier damage and malnutrition in IBD patients.