Gut Microbiota-Mediated Antihypertensive Effects of Probiotic Fermented Milk: A Multi-Omics Study

The precise molecular mechanisms through which gut microbiota mediate the antihypertensive effects of probiotic fermented milk (PFM) remain largely unexplored. This study aimed to elucidate these mechanisms by employing a multi-omics approach, combined with metagenomic deep sequencing technology, non-targeted metabolomics technology, and antibody chip protein detection technology to elucidate the potential mechanisms behind the antihypertensive effects of milk fermented by Lactiplantibacillus plantarum SR37-3 (PFM-SR37-3) in spontaneously hypertensive rats (SHR). Our findings demonstrate that PFM-SR37-3 intervention significantly reduces blood pressure in SHR and is associated with partial inactivation of the renin-angiotensin system (RAS). Notably, long-term administration of PFM-SR37-3 inhibited the progressive rise in systolic blood pressure (SBP), with final measurements of 187.17 ± 3.61 mmHg in the model group versus 172.21 ± 11.81 mmHg in the PFM-SR37-3-treated group after 4 weeks (p < 0.01). PFM-SR37-3 modulates key host metabolic pathways (especially arachidonic acid metabolism) by reshaping the gut microbiota (such as enrichment of Lactobacillaceae), with concomitant reductions in the levels of proinflammatory cytokines (such as ICAM-1 and Fractalkine). This "gut-immune" pathway is an important complement to its partial inhibition of the RAS. Collectively, these data highlight strong associations between PFM-induced gut microbial shifts and antihypertensive effects, providing a multi-faceted view of the potential mechanisms and underscoring the therapeutic potential of PFM in managing hypertension.