Microbial oncogenesis within the gastric niche: how the gastric microbiota influences H. pylori-induced disease progression

Chronic pathogens incur a significant public health burden, contributing to the development of 1 in 5 cancer cases worldwide. <i>Helicobacter pylori</i>, a Gram-negative bacterium that colonizes the gastric mucosa, is the strongest known risk factor for gastric adenocarcinoma, the fifth leading cause of cancer-related mortality. <i>H. pylori</i> colonizes almost half of the world's population; however, despite its high prevalence, only approximately 1-3% of infected individuals progress to this malignancy. These data suggest that <i>H. pylori</i> colonization alone may be insufficient to fully drive oncogenic progression. Previously considered a sterile environment, the stomach is now recognized to harbor a diverse microbial ecosystem, which plays a crucial role in human health and disease. Emerging research highlights the complex interplay between <i>H. pylori</i> and the gastric microbiota, with several commensal bacterial species now identified as modulators of disease progression. Clinical data have defined key variations in gastric microbiota composition between <i>H. pylori</i>-infected individuals who progress toward gastric cancer and those who simply develop gastritis alone, further suggesting that the gastric microbiota affects cancer risk in synergy with <i>H. pylori</i>. In this review, we will discuss microbial species identified within the stomach of <i>H. pylori</i>-infected persons that orchestrate detrimental or protective interactions, which influence the host response and alter cancer risk.