Crohn's Disease Enteritis: Pathophysiological Mechanisms and Therapeutic Approaches

Crohn's disease (CD) is a chronic, relapsing-remitting inflammatory condition of the gastrointestinal tract. This review provides a comprehensive analysis of the underlying pathophysiological mechanisms, highlighting the interplay between intestinal epithelial cells, dysregulated immune responses, gut microbiota and environmental triggers in CD. Key genetic susceptibilities (e.g., NOD2, ATG16L1, IL23R) and dysregulated T-cell signalling, particularly involving T-helper 1 (Th1) and T-helper 17 (Th17) pathways, are central to CD pathogenesis. The progression of the disease is driven by complex cytokine and chemokine networks (e.g., TNF-α, IL-6, IL-17), epithelial barrier dysfunction and microbial dysbiosis, all of which contribute to chronic inflammation and mucosal damage. Advanced models, including organoids and patient-derived xenografts, have elucidated these mechanisms, aiding in biomarker discovery and drug development. Diagnostic advancements such as capsule endoscopy, magnetic resonance enterography, faecal calprotectin and molecular assays enable precise characterization of CD phenotypes and activity. Therapeutic strategies now encompass targeted biologics that neutralize key cytokines, small-molecule Janus kinase (JAK) inhibitors that interrupt intracellular inflammatory signalling and emerging modalities targeting epithelial repair and microbiome restoration. Despite significant progress, challenges persist in managing refractory CD, including loss of response to biologics and fibrostenotic or fistulizing complications. Personalized approaches based on immunological profiling, microbiota composition and molecular diagnostics hold promise for more effective interventions. This review underscores the complexity of intestinal inflammation in CD and advocates for integrated, personalized strategies to improve patient outcomes.