Microbiota-immune crosstalk in the regulation of intestinal motility in constipation.

Constipation is a common functional gastrointestinal disorder with a complex pathogenesis. Traditional studies have primarily explained its development in terms of reduced intestinal motility or impaired defecatory coordination; however, these mechanisms alone cannot fully account for the multifactorial pathological processes underlying the condition. In recent years, increasing attention has been directed toward the roles of intestinal microbial dysbiosis and alterations in immune homeostasis in the development of constipation. The gut microbiota continuously interacts with the intestinal immune system through its structural components, metabolic products, and secreted molecules. These interactions modulate the mucosal immune microenvironment and participate in the regulation of intestinal motility by influencing the enteric nervous system, interstitial cells of Cajal, and smooth muscle function. Conversely, the immune system can reshape the composition and spatial distribution of the gut microbiota through mechanisms such as the mucosal barrier, immunoglobulin A, and antimicrobial peptides, thereby forming a bidirectional regulatory network. Accumulating evidence suggests that during the onset and progression of constipation, microbial dysbiosis, shifts in immune homeostasis, and abnormalities in intestinal motility may evolve through a progressively amplifying dynamic process, ultimately establishing a self-sustaining chronic cycle. In addition, microbiota-targeted interventions-including probiotics, prebiotics, and fecal microbiota transplantation-have demonstrated potential benefits in improving stool frequency and stool consistency in several clinical studies. However, the immunological mechanisms underlying these effects remain relatively underexplored. This review systematically summarizes the molecular mechanisms by which gut microbiota-immune interactions regulate intestinal motility. By integrating current evidence on disease progression and clinical studies, we propose a conceptual model of the "microbiota-immune-motility regulatory axis," aiming to provide a new perspective for understanding the pathogenesis of constipation and for optimizing microbiota-based therapeutic strategies.