Intestinal Barrier Dysfunction in Inflammatory Bowel Disease: Pathophysiology to Precision Therapeutics

Abstract Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is characterized by chronic gastrointestinal inflammation and disruptions in the intestinal barrier, commonly referred to as “intestinal barrier dysfunction.” This phenomenon involves increased intestinal permeability, enabling bacterial toxins, antigens, and other harmful substances to cross the epithelial barrier, exacerbating inflammation and contributing to systemic complications. The underlying mechanisms of intestinal barrier dysfunction in IBD are multifactorial, encompassing genetic predispositions, immune dysregulation, epithelial tight junction protein alterations, and gut microbiota imbalances. This review provides a comprehensive analysis of barrier dysfunction and its role in driving IBD pathogenesis, influencing disease severity, and contributing to extraintestinal complications. We examine current and emerging diagnostic biomarkers such as zonulin, fecal calprotectin, and microbial signatures, while outlining persistent challenges in their standardization and translation into clinical practice. Therapeutic strategies targeting gut barrier restoration spanning anti-inflammatory agents, dietary modifications, and novel microbiota-targeted therapies are critically discussed. The key gaps, particularly whether barrier dysfunction is a primary cause or a secondary consequence of IBD, lack of standardized clinically validated biomarkers, and limited translational efficiency into therapeutic applications, are also discussed. Addressing these gaps by integrating multidisciplinary research and adoption of advanced analytical technologies can pave way for personalized treatments, improving patient outcomes and mitigating the disease burden.