Abstract: PURPOSE: To analyze the effects of S.mutans gavage on blood pressure and intestinal metabolites in angiotensin Ⅱ-induced hypertensive mice, and to identify intestinal metabolic markers associated with hypertension. METHODS: Eight-week-old male C57BL/6J mice were randomly divided into vehicle hypertension(VH) group and S. mutans hypertension(SH) group, each administered with 200 μL sterile PBS or PBS containing 1×10⁹ CFU S.mutans by gavage once daily for 4 weeks. Subsequently, a mouse model of hypertension was induced by subcutaneous infusion of human angiotensin Ⅱ(750 ng/kg/min) for 2 weeks using a mini-osmotic pump, during which the blood pressure of the mice was monitored by non-invasive tail-cuff method. After 2 weeks, feces from both groups of mice were collected, and the intestinal metabolites of the mice were detected by LC-MS/MS untargeted metabolomics technology. RESULTS: Non-invasive tail-cuff blood pressure monitoring showed that compared with the VH group, the systolic and diastolic blood pressures of the SH group were elevated. The results of non-targeted metabolomic analysis of feces by LC-MS/MS showed that there were 237 differential metabolites between the two groups, among which 15 showed significant differences, mainly belonging to lipids and lipid-like molecules, organic acids and their derivatives. There were 6 significantly enriched metabolic pathways (FDR<0.05), with the most enriched pathway being the bacterial ATP-binding cassette transporter pathway, which was related to the intestinal barrier and the generation of intestinal metabolites. CONCLUSIONS: Gavage of S.mutans can significantly alter the composition of intestinal metabolites in hypertensive mice, potentially increasing angiotensin Ⅱ-induced hypertension in mice by modulating the choline-trimethylamine metabolic axis, NO production, and ROS production.

Key words: S. mutans, Hypertension, Angiotensin Ⅱ, Gut metabolomics