Emerging role of Itaconate in inflammatory bowel disease: From multitarget Immunometabolic mechanisms to therapeutic translation.

Itaconate (ITA), as an emerging immunometabolite, has been proven to play a significant protective role in inflammatory diseases like systemic lupus erythematosus, rheumatoid arthritis, and atherosclerosis in recent years. However, its comprehensive regulatory mechanisms and therapeutic potential in inflammatory bowel disease (IBD) remain underexplored. This review focuses on the metabolism-immune regulatory functions of ITA in IBD, elucidating its multi-target mechanisms: reducing the tissue infiltration of innate immune cells; promote the anti-inflammatory phenotypic transformation of M2 in macrophages; inhibit the production of key pro-inflammatory factors; enhance the intestinal epithelial barrier function; and modulating gut microbiota composition and host-microbiota crosstalk. Building upon this mechanistic foundation, this review further explores the potential of ITA as a novel therapeutic strategy for IBD, including its application prospects as a monotherapy, synergistic effects with other existing drugs, and the feasibility of targeting the ITA metabolic pathway as a future drug development direction. In conclusion, it is of paramount to deeply clarify the precise actions of ITA within the complex microenvironment of IBD, which can accelerate the advancement of rigorous clinical research, overcome the current challenges in IBD treatment, and ultimately provide patients with a new option for safer and more effective metabolic immunotherapy.