Beyond acid suppression: the multifaceted role of proton pump inhibitors in Helicobacter pylori eradication.

Gastric acid is essential for digestion, host defense, and maintenance of gastrointestinal homeostasis; however, its excessive or inappropriate secretion contributes to the development and progression of several acid-related disorders. Proton pump inhibitors (PPIs) have remained the cornerstone of acid-suppressive therapies for more than four decades owing to their potent blockade of gastric H+/K+-ATPases. This review provides a comprehensive overview of the pharmacological properties, clinical applications, and current limitations of the most widely used PPIs, including omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, and rabeprazole. Particular emphasis is placed on their role in the management of Helicobacter pylori infection, a strong risk factor for the development of severe gastric diseases and one of the most clinically important indications for PPI-based antibiotic therapy. Beyond elevating intragastric pH to enhance antibiotic stability and efficacy, accumulating evidence indicates that PPIs exert direct antibacterial activity against H. pylori and may act synergistically with selected antibiotics. The review also discusses emerging evidence for interindividual variability in PPI metabolism, drug-drug interactions, and concerns regarding long-term adverse effects of the current treatments. Finally, it highlights potassium-competitive acid blockers (P-CABs), a newer class of acid-suppressive agents that provide sustained acid inhibition and represent a promising alternative to PPI-based regimens for H. pylori eradication.