Diamine Oxidase and Gastrointestinal Diseases

Histamine plays an essential role in gastrointestinal physiology and immune control, while its balance in the intestinal environment is largely maintained through degradation by diamine oxidase (DAO), a copper-dependent enzyme mainly produced by differentiated enterocytes. Impaired DAO activity reduces the intestinal barrier to luminal histamine, leading to increased local and systemic exposure and contributing to altered motility, permeability, visceral sensitivity, and immune activation. Accumulating research suggests that disturbances in diamine oxidase regulation contribute to the development of various gastrointestinal diseases, including histamine intolerance, inflammatory and functional bowel disorders, intestinal ischemia, and liver pathology. This review summarizes current knowledge on the biochemistry, localization, and regulation of DAO, as well as histamine signalling via H1–H4 receptors in the gastrointestinal tract. We highlight the interaction between epithelial injury, immune activation, dysbiosis, and histamine accumulation, and discuss the divergent interpretation of mucosal versus circulating DAO activity. Finally, we critically assess the diagnostic limitations of serum DAO and explore emerging therapeutic strategies targeting impaired histamine degradation. Although DAO represents a promising adjunctive biomarker and therapeutic target, its clinical utility requires standardized measurement methods and integrative diagnostic approaches.