The Extragastric Burden of Helicobacter pylori

Abstract Helicobacter pylori is a Gram-negative, microaerophilic, spiral-shaped bacterium that colonizes the gastric mucosa of approximately half of the world’s population. Although historically regarded as a purely gastric pathogen responsible for gastritis, peptic ulcer disease and gastric malignancies, a substantial body of evidence accumulated over the past decades has established that its impact extends far beyond the stomach. Extragastric manifestations include hematological, cardiovascular, neurological, endocrine, dermatological, hepatobiliary, respiratory, obstetric, and other systems. The pathogenic mechanisms are unified by four overlapping pathways: chronic low-grade systemic inflammation, molecular mimicry driven by cytotoxin-associated gene A and bacterial heat shock protein 60, nutrient malabsorption secondary to hypochlorhydria, and immune dysregulation. The evidence is strongest for iron-deficiency anemia, immune thrombocytopenic purpura, vitamin B12 deficiency, and chronic spontaneous urticaria, whereas associations with neurodegenerative, metabolic, and obstetric disorders represent rapidly expanding areas of research. This review integrates contemporary evidence on the principal extragastric manifestations of H. pylori , outlines proposed mechanisms, and summarizes the impact of eradication therapy.