Inflammatory Bowel Disease: Mechanisms and Therapeutic Advances

ABSTRACT

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, represents a chronic, immune‐mediated pathology in which genetic susceptibility, environmental exposures, and microbial perturbations converge to destabilize intestinal homeostasis. Despite a steady global rise in incidence affecting more than 10 million people worldwide, current single‐pathway biologic and small‐molecule therapies still leave 30–40% of patients without durable remission, with progression to stricturing, fistulizing, or transmural complications. Yet the mechanistic integration of innate and adaptive immune networks, epithelial barrier dysfunction, and microbiota‑driven inflammation remains fragmented. This review summarizes recent advances in understanding the pathophysiological mechanisms driving IBD, focusing on innate and adaptive immune networks. Current therapies, including cytokine or integrin‐targeting biologics and small‐molecule inhibitors like Janus Kinase (JAK) antagonists, are critically evaluated in light of their restricted pathway coverage. In response to these challenges, emerging strategies are examined targeting nonimmune pathways, including microRNA‑124‐mediated gene regulation, fecal microbiota transplantation, and mesenchymal stromal cell therapies that combine immunomodulation with tissue repair. The development of effective IBD therapies is likely to benefit from combining complementary treatment strategies, guided by molecular and cellular profiling. This review underscores a paradigm shift from monotherapies to integrated, multitarget approaches as the new frontier in IBD management.