Intestinal Barrier Dysfunction in Ulcerative Colitis: Mechanisms and Therapeutic Perspectives

Abstract

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease characterized by persistent mucosal inflammation of the colon and rectum. Although the exact etiology of UC remains incompletely understood, accumulating evidence suggests that intestinal barrier dysfunction plays a central role in disease initiation, progression, and recurrence. The intestinal barrier is a complex system composed of the epithelial layer, tight junction proteins, mucus layer, immune components, and gut microbiota, which together maintain mucosal homeostasis and protect against luminal pathogens and antigens. In UC, impairment of epithelial integrity, altered tight junctions, goblet cell depletion, mucus layer defects, microbial dysbiosis, and exaggerated immune activation contribute to increased intestinal permeability and sustained inflammation. Recent studies have highlighted multiple mechanisms underlying barrier dysfunction in UC, including inflammatory cytokine-mediated signaling, oxidative stress, mitochondrial injury, and dysregulated cell death pathways. Moreover, restoration of barrier integrity has emerged as an important therapeutic goal. Conventional anti-inflammatory agents, biologics, small-molecule compounds, microbiota-based therapies, and several emerging approaches may exert beneficial effects at least partly through improving barrier function. In this review, we summarize the structural and functional components of the intestinal barrier, discuss the major mechanisms of barrier dysfunction in UC, and highlight current and potential therapeutic strategies targeting barrier restoration. A better understanding of intestinal barrier impairment may provide new insights into the pathogenesis of UC and facilitate the development of more effective and personalized treatment approaches.