Ferroptosis in Gastrointestinal Diseases: A New Frontier in Pathogenesis and Therapy

Abstract

Ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a key player in the pathogenesis of gastrointestinal (GI) diseases. Unlike apoptosis or necrosis, ferroptosis is characterized by distinctive metabolic and molecular pathways, including dysregulated iron metabolism, oxidative stress, and impaired antioxidant defenses. This review explores the complex role of ferroptosis in conditions such as inflammatory bowel disease (IBD), non-alcoholic steatohepatitis (NASH), and gastrointestinal cancers. Special attention is given to the molecular mechanisms underlying ferroptosis, including the Xc−/GSH/GPX4 axis, ferritinophagy, ACSL4/LPCAT3-mediated lipid remodeling, and the influence of the gut microbiota. Therapeutic strategies targeting ferroptosis—including pharmacological inhibitors, iron chelators, and microbiota-based interventions—are evaluated for their translational potential, underscoring ferroptosis as a promising target for precision therapies in gastroenterology and highlighting the need for further clinical studies to validate its diagnostic and therapeutic implications.