Novel targets for mucosal healing in inflammatory bowel disease therapy

Inflammatory bowel disease (IBD) is a chronic condition affecting the gastrointestinal tract, primarily manifesting as ulcerative colitis (UC) or Crohn's disease (CD). Both inflammation and disruption of the intestinal epithelial barrier are key factors in IBD pathogenesis. Substantial evidence has revealed a significant association between aberrant immune responses and impairment of the intestinal epithelial barrier in IBD pathogenesis. The components of the intestinal epithelium, particularly goblet cells and Paneth cells, are crucial to gut homeostasis, as they secrete mucin, antimicrobial peptides (AMPs), and cytokines. Furthermore, impairment of epithelial integrity, which is regulated by tight junctions, is a hallmark of IBD pathology. While common treatments for IBD, such as anti-inflammatory drugs, target various signaling pathways with varying efficacies, therapeutic approaches focused on mucosal and epithelial barrier healing have been largely neglected. Moreover, high costs, side effects, and insufficient or inconsistent therapeutic outcomes remain major drawbacks of conventional anti-IBD drugs. Recent studies on epithelial barrier regeneration and permeability reduction have introduced promising therapeutic targets, including farnesoid X receptor (FXR), urokinase-type plasminogen activator (uPA)-urokinase-type plasminogen activator receptor (uPAR) interaction, fecal microbiota transplantation (FMT), and insulin receptor (INSR). Notably, the simultaneous targeting of intestinal inflammation and promotion of epithelial barrier healing shows promise for efficient IBD treatment. Future research should explore targeted therapies and combination treatments, including natural remedies, microbiota colonization, stem cell approaches, and computer-aided drug design. It is also crucial to focus on accurate prognosis and developing a thorough understanding of IBD development mechanisms.