Impaired lower esophageal sphincter (LES) function and transient lower esophageal sphincter relaxations (TLESRs)

Imbalance between gastric mucosal protective and destructive factors such as H. pylori infection and NSAID use

Colonic wall structure, colonic motility, diet, fiber intake, obesity and physical activity

Defects in the epithelial barrier, immune response, leukocyte recruitment, and microflora of the colon