Abstract:Functional constipation is a common functional gastrointestinal disorder with a multifactorial and incompletely understood pathogenesis. Recent studies have revealed that its development involves the interplay of multiple mechanisms, including neurogenic and myogenic dysfunction of the colon, reduction and impairment of interstitial cells of Cajal (ICCs), outlet obstruction, dysregulation of the gut-brain axis, immune activation, and gut microbiota imbalance. Slow-transit constipation is mainly associated with enteric neural abnormalities, disruption of ICC signaling, and inflammation, whereas outlet obstruction constipation often results from pelvic floor dysfunction and rectal hyposensitivity. Dysregulation of the gut-brain axis plays a central role, involving impaired central regulation, hormonal imbalance, and enhanced local immune response. Additionally, gut microbial metabolites such as short-chain fatty acids, bile acids, and methane affect colonic motility and inflammation. This review summarizes the current understanding and research progress on the pathogenesis of functional constipation, providing insights for mechanism-based and individualized therapeutic approaches.