Macrophage immunometabolism in inflammatory bowel diseases: From pathogenesis to therapy

Inflammatory bowel disease (IBD), comprised of ulcerative colitis and Crohn's disease, is a chronic relapsing inflammatory disease of the gastrointestinal tract that closely related to immune dysfunction. Macrophages are the key gatekeeper of intestinal immune homeostasis and have vital influence on IBD. Hence, macrophages have been recognized as attractive targets to develop new therapeutic approaches for the disease. Recently, the growing field of immunometabolism has reinforced that metabolism reprogramming is a key determinant that dictates macrophage functions and subsequent disease progression. Herein, we elaborated how metabolic alterations underlie intestinal macrophage phenotype and function during IBD, and how microenvironmental cues trigger their metabolic reprogramming processes. More importantly, we deciphered the distinguishing characteristic of macrophage immunometabolism in IBD from other inflammatory diseases, and also summarized potential therapeutic approaches for IBD by manipulating cellular metabolism of macrophages. Finally, we discussed the major opportunities and challenges of harnessing metabolism to modulate aberrant macrophage responses in IBD. Altogether, our overview provides a framework for understanding the critical roles and potential therapeutic targets of macrophage immunometabolism in IBD.