What we know about prostaglandin pathway dysfunction in chronic enteropathies: From endoscopy to molecular diagnosis

Chronic enteropathies characterized by multiple superficial ulcers of the small intestine have long been under-recognized, particularly in their early stage. However, the occurrence of refractory occult bleeding and episodes of partial bowel obstruction in this disease severely impacts quality of life, while targeted therapeutic options remain limited. Although dysfunction of the prostaglandin metabolic pathway has been associated with mucosal damage, the underlying molecular mechanisms and potential therapeutic targets remain unclear. In recent years, in-depth investigations of nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy, along with the discovery of rare monogenic disorders affecting the prostaglandin metabolic pathway, have helped bridge this knowledge gap. A broader concept, termed "prostaglandin-associated enteropathy (PGAE)", has since emerged, representing a monumental breakthrough in the differential diagnosis of nonspecific small intestinal ulcers. This narrative review focuses on prostaglandin metabolism and chronic intestinal ulcers, including NSAID-induced enteropathy and chronic enteropathies associated with solute carrier organic anion transporter family member 2A1 (SLCO2A1) and phospholipase A2 group IVA (PLA2G4A). By unraveling molecular connections and highlighting innovative therapeutic avenues, we aim to advance clinical management and improve the well-being and quality of life for patients with PGAE.