Cellular pathogenesis of gastroparesis

Gastroparesis is a complex neuromuscular disorder characterized by delayed emptying of gastric contents. Abnormalities in distribution and function of enteric nerves, interstitial cells of Cajal (ICC), fibroblast-like cells, smooth muscle cells (SMC) and more recently the immune cells within the muscular layers of the stomach have been described. Of these cellular abnormalities, loss of ICC has been shown to be the signature defect which likely results from oxidative and paracrine mediators from pro-inflammatory immune cells, particularly macrophages. Both mice and human studies have shown loss of CD206⁺ anti-inflammatory macrophages in the gastric muscle and their association with ICC loss. Additionally, transcriptomic and proteomic studies have also identifying a macrophage-based immune dysregulation as central to the pathophysiology of human gastroparesis. Future studies should be aimed at determining the immune-enteric nervous system interactions and developing disease-modifying approaches to prevent or treat delayed gastric emptying.