PPAR beta/gamma mediates the antihypertensive activity of a synbiotic preparation of Bifidobacterium lactis and Lactobacillus acidophilus in spontaneous hypertensive rats

PPARβ/γ介导乳双歧杆菌和嗜酸乳杆菌合生元制剂在自发性高血压大鼠中的抗高血压活性

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作者:Ying Huang, Fang Wang, Wei Gong, Yufeng Chen

Background

Hypertension is a global public health concern. A synbiotic preparation containing Bifidobacterium lactis and Lactobacillus acidophilus has been used as adjunct therapy for hypertension. We sought to elucidate the antihypertensive activity of this preparation and explore the underlying mechanisms.

Conclusion

The results of the study suggest that the novel synbiotic preparation reduces blood pressure by altering the composition of the intestinal microbiota, regulating PPAR signaling pathway, and activating the PPARβ and PPARγ cascade reactions in the ileum.

Results

Blood pressure in rats was measured using the tail-cuff method. Colonization of the gastrointestinal tract by the two probiotics was determined by real-time quantitative polymerase chain reaction (qPCR). Mechanistic studies were performed by proteomic analyses based on liquid chromatography-mass spectrometry and STRING database and metabolomic analyses using the UHPLC-Q-TOF/MS platform and peroxisome proliferator-activated receptor (PPAR)β/γ antagonists. Although biochemical analysis of blood samples showed that the synbiotic preparation did not alter the levels of angiotensin II, aldosterone, or cortisol, it significantly lowered the systolic blood pressure in the treatment group. Moreover, the synbiotic preparation contributed to the localization of the two probiotics in the ileum and colon of the treatment group. Proteomics, immunochemistry, and real-time qPCR analyses showed that administration of the synbiotic preparation activated the PPAR signaling pathway in the ileum and significantly upregulated PPARβ and PPARγ. The antagonist studies further confirmed this finding. In addition, metabolomic analyses demonstrated that among the 27 metabolites that showed significant differences between the control and model groups, administration of the synbiotic preparation significantly upregulated lysophosphatidylethanolamine and phosphatidylcholine in the ileum of the treatment group.

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