Curing inflammatory bowel diseases: breaking the barriers of current therapies– emerging strategies for a definitive treatment

Chronic intestinal inflammation in inflammatory bowel diseases (IBD) reflects the interplay of genetic predisposition, immune dysregulation, microbial imbalance, and epithelial barrier defects. Current therapies for IBD primarily focus on controlling inflammation necessitating lifelong treatment and face a ‘therapeutic ceiling’ due to primary and secondary loss of efficacy over time. Immune-mediated approaches do not address additional pathogenic mechanisms, such as impairment of epithelial barrier and gut microbial ecology. Thus, innovative strategies are required to foster the field closer to a definitive cure. This review discusses novel strategies to overcome current therapeutic limitations, including immune reset via hematopoietic stem cell transplantation and B cell–targeted therapies, antigen-specific interventions such as chimeric antigen receptor T cells and tolerogenic vaccines, and intestinal epithelial barrier restoration. We also explore microbiota-based strategies — ranging from fecal microbiota transplantation to engineered consortia and bacteriophages — and discuss the adjunctive role of diet. Together, we outline a potential research roadmap toward a potential cure for IBD.