The Crosstalk Role of Intestinal Barrier Damage in the Gut-Organ Axis and its Potential Therapeutic Implications

Intestinal barrier damage is a pivotal mediator of gut-organ crosstalk and a key contributor to systemic disease. This review systematically summarizes the structural organization of the intestinal barrier, including the mucus layer, epithelial tight junctions, and the lamina propria immune network, and highlights their coordinated roles in regulating intestinal barrier dysfunction and immune homeostasis. Disruption of barrier integrity facilitates the translocation of microbial products, cytokines, and metabolites, thereby promoting systemic inflammation and the pathogenesis of multi-organ diseases, including liver injury, pancreatitis, and cardiovascular disorders. Emerging evidence underscores the critical roles of gut microbiota, immune signaling pathways, and metabolic factors in barrier regulation. Advances in single-cell and spatial omics, together with artificial intelligence (AI)-driven multi-omics integration, are providing novel insights into the cellular heterogeneity and molecular mechanisms underlying barrier dysfunction. Therapeutic strategies targeting barrier restoration—including microbiota-based interventions and pharmacological approaches—show promising potential but require further clinical validation. This review provides a comprehensive framework for understanding intestinal barrier biology and its translational relevance.