Specialized pro-resolving lipid mediators in gut immunophysiology: from dietary precursors to inflammation resolution

Purpose of review This review aims to examine recent research on the role of specialized pro-resolving mediators (SPMs) in the regulation of gut immunophysiology. Recent findings Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gastrointestinal tract, driven by disruptions in the intestinal barrier and an imbalance between the host immune system and gut microbiota. Dietary polyunsaturated fatty acids (PUFAs), especially ω-3 and ω-6, are key regulators of immune responses and help maintain the integrity of the intestinal barrier. These PUFAs serve as precursors to SPMs, lipid mediators that play a critical role in resolving inflammation. SPMs actively reprogram immune cells, promoting the clearance of cellular debris, reducing cytokine production, and restoring tissue homeostasis without suppressing the immune response. Emerging evidence indicates that in the gut, SPMs strengthen intestinal barrier function, modulate immune responses in colitis and colon cancer, and influence gut microbiota composition. Summary The recent evidence strongly supports the central role of SPMs in maintaining gut health and restoring organ function following inflammatory challenges. This evidence highlights the potential of therapeutic approaches that target these pathways for both the prevention and treatment of gut-related inflammatory conditions.