Synergistic gut microbiome-host lipid axis underlies the antihypertensive effect of Qianyang Yuyin formula.

Abstract

BACKGROUND: Prehypertension (Pre-HTN) is highly prevalent and substantially increases the risk of developing hypertension and cardiovascular disease. Gut microbiota (GM) dysbiosis and altered lipid metabolism are increasingly recognized as critical regulators of blood pressure (BP). Traditional Chinese Medicine (TCM) formulas, such as Qianyang Yuyin Granules (QYYY), offer multi-target interventions, yet their preventive mechanisms in Pre-HTN remain unclear. PURPOSE: This study aimed to investigate the antihypertensive effects of QYYY and elucidate its underlying mechanisms in a prehypertensive rat model. METHODS: Prehypertensive spontaneously hypertensive rats (SHRs) were treated with QYYY for four weeks. Multi-omics analyses, including metagenomics, plasma metabolomics, and transcriptomics, were conducted. Causal involvement of GM was tested using antibiotic-induced pseudo-germ-free SHRs with fecal microbiota transplantation (FMT) from QYYY-treated donors, administered alone or in combination with QYYY. Gut barrier integrity, systemic inflammation, and vascular function were evaluated by histology, immunofluorescence, transmission electron microscopy, and ELISA. RESULTS: QYYY significantly lowered SBP and DBP, reversed GM dysbiosis, normalized the Firmicutes/Bacteroidetes ratio, and modulated differential bacteria including Frisingicoccus and Blautia. These microbial shifts correlated with restoration of lysophosphatidylethanolamines (LPEs), inversely associated with BP, revealing a GM-lipid-BP axis. FMT alone was insufficient, whereas the combination of FMT+QYYY produced the strongest antihypertensive effect, restoring intestinal barrier integrity, enhancing ZO-1 expression, and normalizing Ang-II and NO levels. Transcriptomic analyses suggested PPAR and ROS signaling pathways as potential mechanisms mediating the antihypertensive effect of QYYY. CONCLUSION: QYYY prevents BP elevation in Pre-HTN via synergistic microbiota-dependent and independent mechanisms, offering a comprehensive strategy for early hypertension prevention.