The role of metabolic crosstalk between Intestinal epithelial cells and immune cells in inflammatory bowel disease and targeting strategies.

Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory disorder characterized by disruption of the intestinal epithelial barrier and dysregulated immune responses. IBD pathogenesis is intricately linked to the metabolic reprogramming of the intestinal epithelial cells (IECs), which are central to both barrier maintenance and immune crosstalk. Mitochondrial dysfunction in the IECs leads to energy deficit, oxidative stress, and barrier failure, which activates the adjacent immune cells and establishes a vicious cycle of inflammation. This review focuses on the key role of the mitochondrial metabolism in IBD with a specific focus on the remodeling of the glucose, lipid, and amino acid metabolic pathways in epithelial and immune cells. We elaborate on the specific regulatory mechanisms underlying these metabolic processes and the functions of metabolic products as signaling molecules in cell-cell communication. In addition to causing energy crises and barrier defects in epithelial cells, metabolic remodeling directly controls the activation of immune cells and their polarization toward a pro-inflammatory phenotype. Thus, a deeper understanding of mitochondrial metabolism underlying IBD would provide a crucial theoretical foundation for developing novel precision therapies targeting metabolism. Additionally, elucidating these metabolic networks would provide new therapeutic opportunities for restoring homeostasis in IBD.