Macrophage targeting offers new theoretical approaches for treating gastrointestinal motility disorders and constipation

Gastrointestinal motility disorders are pathologically characterized by dysregulation of the tripartite network comprising the intestinal immune system, the enteric nervous system, and the gut microbiota. Targeted medicines that target important nodes in this network are desperately needed, and macrophages—tissue-resident immune cells with a high degree of plasticity—are showing promise as therapeutic targets. Through functional polarization, macrophages serve a key role in controlling intestinal inflammation and motility by integrating various signals from immune cells, pathogens, and neurons. According to new research, macrophages have two roles in gastrointestinal motility disorders: on the one hand, abnormal polarization can lead to immunological dysregulation and neuronal damage, which exacerbates motility dysfunction; on the other hand, certain subsets of macrophages aid in tissue repair and homeostasis. A thorough study that methodically outlines the pathogenic processes and therapeutic possibilities of macrophages in gastrointestinal motility disorders is still absent, despite recent advancements. In addition to evaluating new treatment approaches that target macrophage polarization, phagocytic function, and neuro-immune interaction, this review summarizes the unique mechanistic functions of macrophages in situations such postoperative ileus, constipation, and disorders of gut-brain interactions. In addition to offering theoretical insights and fresh approaches for precision intervention in gastrointestinal motility disorders, our goals are to expand on the present knowledge of the gut neuro-immune–microbiota regulating network.