Glutathione peroxidase in inflammatory bowel disease: From ferroptosis, immunity, and microbiota regulation to targeted nanomedicines.

Inflammatory bowel disease (IBD) is a complex, chronic, immune-mediated intestinal disorder whose pathogenesis is intrinsically linked to oxidative stress, gut dysbiosis, and ferroptosis. As a key antioxidant enzyme family, glutathione peroxidase (GPX) comprises selenium-dependent selenoproteins and cysteine-based non‑selenium homologs, which maintain intracellular redox homeostasis. By efficiently reducing hydrogen peroxide as well as organic and lipid hydroperoxides, GPX suppresses lipid peroxidation and ferroptosis, thereby safeguarding the integrity of the intestinal epithelial barrier and maintaining gut microbiota stability. Patients with IBD frequently exhibit reduced selenium levels and diminished GPX activity, with GPX expression showing a strong correlation with disease activity. Emerging GPX-targeted intervention strategies, including pharmacological agents and nanomedicine formulations, have demonstrated promising therapeutic efficacy in preclinical experimental models. This review summarizes the functional characteristics of GPX, its mechanistic roles in IBD, and prospective therapeutic directions, providing a valuable reference for future research.