Mechanisms by which tryptophan metabolites enhance intestinal barrier function to prevent necrotizing enterocolitis...

Necrotizing enterocolitis (NEC) is one of the most severe intestinal diseases affecting preterm infants, characterized by high mortality rates and significant long-term complications, which present substantial challenges to clinical management. The primary pathological mechanism underlying NEC is the immature development of the intestinal barrier in preterm infants, which fails to adequately resist luminal pathogen invasion, triggering uncontrolled inflammatory responses and tissue damage. Additionally, intestinal dysbiosis further compromises the integrity of the intestinal barrier. In recent years, growing attention has been given to the role of tryptophan metabolites in maintaining intestinal barrier integrity. As an essential amino acid, tryptophan metabolites-particularly those derived from gut microbiota, such as indole compounds-have been shown to exert significant barrier-protective effects through multiple mechanisms, including the activation of the aryl hydrocarbon receptor (AhR), upregulation of tight junction protein expression, inhibition of inflammatory responses, and promotion of epithelial cell repair. This review aims to summarize the major biological pathways of tryptophan metabolism, with particular emphasis on the molecular mechanisms by which microbial indole derivatives enhance the physical, chemical, and immune barriers. By synthesizing both preclinical studies and clinical evidence, this article explores the translational potential of tryptophan metabolite-targeted strategies for NEC prevention, providing a theoretical foundation for the development of precise preventive interventions.