The Intestinal Macrophage-Intestinal Stem Cell Axis in Inflammatory Bowel Diseases: From Pathogenesis to Therapy

The gut plays a crucial role in digestion and immunity, so its balance is essential to overall health. This balance relies on dynamic interactions between intestinal epithelial cells, immune cells, and crypt stem cells. Inflammatory bowel disease (IBD), which consists of ulcerative colitis and Crohn's disease, is a chronic relapsing inflammatory disease of the gastrointestinal tract closely related to immune dysfunction. Stem cells, known for their ability to self-renew and differentiate, play an important role in repairing damaged intestinal epithelium and maintaining homeostasis in vivo. Macrophages are key gatekeepers of intestinal immune homeostasis and have a significant impact on IBD. Current research has focused on the link between epithelial cells and stem cells, but interactions with macrophages, which have been recognized as attractive targets for the development of new therapeutic approaches to disease, have been less explored. Recently, the developing field of immunometabolism has reinforced that metabolic reprogramming is a key determinant of macrophage function and subsequent disease progression. The aim of this review is to explore the role of the macrophage-stem cell axis in the maintenance of intestinal homeostasis and to summarize potential approaches to treating IBD by manipulating the cellular metabolism of macrophages, as well as the main opportunities and challenges faced. In summary, our overview provides a framework for understanding the critical role of macrophage immunometabolism in maintaining gut health and potential therapeutic targets.