Intestinal alkaline phosphatase and gut health: insights into homeostasis, barrier protection, and immune signaling

Abstract

Intestinal alkaline phosphatase (IAP) is a brush border enzyme critical for maintaining gut homeostasis by detoxifying bacterial endotoxins, regulating nutrient metabolism, and modulating immune responses. IAP activity is modulated by dietary components such as carbohydrates, fats, probiotics, and vitamins, and has a dose-dependent effect. It strengthens intestinal barrier function by upregulating tight junction proteins and mitigating inflammation via lipopolysaccharide (LPS) detoxification and immunomodulatory pathways. Emerging evidence highlights its pleiotropic roles in intestinal barrier protection, microbiota regulation, and inflammation modulation, positioning IAP as a potential therapeutic target for gastrointestinal and systemic disorders, including inflammatory bowel disease (IBD), necrotizing enterocolitis (NEC), and metabolic syndrome. This review synthesizes current knowledge on IAP's biological functions, focusing on its interactions with dietary components, gut microbiota, and critical signaling pathways. It explores innovative delivery systems such as liposomes, hydrogels, and exosomes to enhance IAP stability and bioavailability, alongside artificial intelligence (AI)-driven personalized nutrition strategies to optimize IAP activity. Future research should focus on bridging molecular mechanisms with clinical applications to harness IAP's full potential in promoting gut health and preventing disease.