Folate-producing Lactiplantibacillus plantarum TXZ 2–26 attenuates H-type hypertension by reshaping gut microbiota and metabolic profiles

H-type hypertension, characterized by hyperhomocysteinemia and folate deficiency, is influenced by gut microbiota dysbiosis. Supplementation with folate-producing probiotics may offer a therapeutic strategy, but its mechanisms require clarification. Using a hypertensive mouse model induced by L-NAME/high-salt, we evaluated the effects of two Lactiplantibacillus plantarum strains: the high folate-producer TXZ 2–26 and a low-producer control, F4–1. Only TXZ 2–26 significantly attenuated elevations in systolic and diastolic blood pressure, reduced renal inflammation and fibrosis, and improved metabolic parameters. This was accompanied by a reversal of hypertension-associated gut dysbiosis—specifically, a decrease in pro-inflammatory taxa (e.g., Porphyromonadaceae ) and an increase in beneficial microbes (e.g., Muribaculaceae ).Metabolomic analysis revealed that TXZ 2–26 restored host metabolic pathways related to amino acid and lipid metabolism. Crucially, TXZ 2–26 treatment significantly increased folate levels and decreased homocysteine (HCY) in both feces and serum, establishing a strong inverse correlation between them. HCY levels were, in turn, positively correlated with blood pressure. Our findings demonstrate that the antihypertensive effect of L. plantarum TXZ 2–26 is specifically dependent on its high folate-producing capacity, which modulates the gut microbiota, reprograms host metabolism, and corrects the folate-HCY axis imbalance. • High folate-producing L. plantarum TXZ 2–26 lowers blood pressure and alleviates renal injury in H-type hypertension. • TXZ 2–26 modulates gut microbiota composition by reducing pro-inflammatory taxa and enriching beneficial microbes. • TXZ 2–26 restores host metabolism and the folate-HCY axis, providing mechanistic insight into its antihypertensive effects.