Decoupling Ecological and Pathogenic Roles: Helicobacter pylori as a Gastric Hegemon Maintaining Order or Amplifying...

Gastric dysbiosis refers to disease-associated alterations in microbial composition and between-individual variability. We postulate that Helicobacter pylori (H. pylori or Hp) exerts a context-dependent ecological effect across the Correa cascade-the histopathological progression from chronic gastritis through atrophic gastritis and intestinal metaplasia to gastric cancer-by constraining microbiome variation when acting alone but amplifying disease-associated divergence as pathology advances. We reanalyzed 756 gastric 16S rRNA gene profiles using Hill-number beta diversity and the Anna Karenina principle across three complementary schemes: (1) comparison of H. pylori infection status within each disease stage (Scheme-I); (2) disease progression in the Hp-negative cohorts, from healthy controls to successive disease stages (Scheme-II); and (3) disease progression in the Hp-positive, from healthy controls to successive disease stages (Scheme-III). We find: H. pylori alone consistently reduced microbiome divergence across disease stages, indicating a homogenizing effect rather than direct induction of dysbiosis. In contrast, progression to gastric cancer was the strongest driver of divergent dysbiosis, even in the absence of the bacterium. Most importantly, the presence of H. pylori caused dysbiotic divergence to emerge in multiple precancerous disease stages. These findings identify H. pylori as a context-dependent ecosystem modifier that maintains order in isolation but amplifies disease-associated dysbiosis.