Pathogenesis of Microscopic Colitis: Current Insights

Abstract— Microscopic colitis (MC) is a chronic inflammatory bowel disease characterized by watery, non-bloody diarrhea and a normal endoscopic appearance, necessitating histopathological evaluation for diagnosis. Despite increasing recognition, its pathogenesis remains incompletely understood. This review synthesizes current evidence on the genetic, immunological, and luminal factors contributing to MC. Genetic susceptibility plays a crucial role, particularly the association with HLA-DQ2 haplotypes and select non-HLA polymorphisms, suggesting a distinct immune-mediated background. Immunologically, MC is marked by mucosal infiltration of CD8⁺ T cells, Th1/Tc1 and Th17/Tc17 cytokine profiles, and enhanced local cellular proliferation, driving mucosal inflammation. Luminal influences, including altered gut microbiota composition, reduced microbial diversity, and dysregulation of bile acid signaling pathways—especially those involving farnesoid X receptor (FXR)—further compromise epithelial integrity and perpetuate immune activation. These findings underscore the multifactorial nature of MC, integrating host genetics, mucosal immunity, and environmental triggers. Understanding these mechanisms not only delineates MC as distinct from classical inflammatory bowel diseases but also provides a foundation for developing targeted therapeutic strategies. Approaches modulating the gut microbiota or bile acid pathways may represent promising directions to improve disease management and patient outcomes in microscopic colitis.