Saliva-driven surface-engineered Bacteroides thetaiotaomicron alleviates hypertension

Oral environment is closely linked to blood pressure regulation. However, the underlying mechanisms remain poorly understood, and strategies for harnessing this relationship to modulate blood pressure are still scarce. Saliva, abundant in the oral cavity, was demonstrated to play a critical role in sustaining the abundance of gut Bacteroides thetaiotaomicron (Bt), contributing to blood pressure reduction. Metal ions and mucins in saliva were further identified as factors responsible for Bt growth. Building on this discovery, we developed a saliva-inspired, surface-engineered Bt (Bt–FM) that reconstructs the cooperative microenvironment formed by metal ions and mucins in natural saliva. The biomimetic Fe 2+ –chitosan–mucin (FM) layer recapitulates both the protective and regulatory features of saliva, enabling Bt to maintain structural integrity and metabolic activity under gastrointestinal stress. This design transforms salivary cues into a functional engineering strategy that enhances Bt stability, colonization, and antihypertensive efficacy in vivo. Further exploration revealed that anti-hypertensive effects involve synthesizing short-chain fatty acids, modulating sodium ion channels, and maintaining gut immune homeostasis. This work pioneers a dynamic, material-based platform to probiotic enhancement for hypertension management. Saliva administered to hypertensive mice enhanced gut colonization of Bacteroides thetaiotaomicron and reduced blood pressure. Inspired by saliva's mucin- and metal ion–mediated effects, a chitosan–Fe 2+ –mucin multilayer coating generated surface-engineered Bt-FM with enhanced viability, which ameliorated hypertension via SCFAs, α-ENaC modulation, and immune regulation. • Bacteroides thetaiotaomicron was supported by salivary factors and associated with blood pressure regulation. • A saliva-driven Fe 2+ -chitosan-mucin coating was designed to enhance Bacteroides thetaiotaomicron viability and functionality. • The surface engineering strategy was inspired by the growth-promoting effects of salivary metal ions and mucins. • The engineered probiotic alleviated hypertension via SCFAs, sodium channel modulation, and gut immune balance.