Underlying Mechanisms of Helicobacter pylori in Caries Progression and the Corresponding Dual-Responsive Hydrogel-Based Intervention

Helicobacter pylori (H. pylori) infects nearly half of the global population. Given that H. pylori is considered poorly adapted to the oral environment, previous studies have mainly focused on gastric infection. By contrast, how H. pylori persists in the oral cavity and relates to oral diseases remains unclear. This study investigates the role of H. pylori in caries progression. The results show that H. pylori is retained within Streptococcus mutans (S. mutans) biofilms, and its presence is associated with transcriptional remodeling in S. mutans, alongside increased overall cariogenic potential of the mixed biofilm. In a rat caries model, H. pylori co-colonization aggravates caries progression and oral microbiota dysbiosis. To address this pathological niche, a multifunctional hydrogel, termed GPAM, is designed by integrating a Cu₂O@Pt heterojunction (MCP) with amorphous calcium phosphate (ACP). Under activation by yellow light and ultrasound, MCP generates reactive oxygen species (ROS) to disrupt S. mutans-H. pylori mixed biofilms. Meanwhile, released Cu²⁺ reduces H. pylori urease activity, and ACP promotes tooth remineralization. GPAM also shows microbiota-modulating potential. Together, these findings provide insight into H. pylori-associated caries progression and support GPAM as a multifunctional therapeutic strategy for mixed biofilms and caries-related damage.