The primary cause of peptic ulcer disease is Helicobacter pylori, a gram-negative, spiral-shaped bacterium that colonizes the gastric mucosa. It disrupts the protective mucus layer by producing urease, which neutralizes gastric acid, allowing bacterial survival and leading to chronic inflammation. This inflammation damages the mucosal lining, resulting in ulcers primarily in the stomach and duodenum. Eradication of H. pylori is essential to promote ulcer healing and prevent recurrence. Unlike other organisms, H. pylori uniquely adapts to the acidic gastric environment, making it the key pathogen in peptic ulcer disease.

Reference: Harrison's Principles of Internal Medicine, Jameson et al., 20th Edition.