Yuan Lin, Li Ying, Chen Moutong, Xue Liang, Wang Juan, Ding Yu, Zhang Jumei, Wu Shi, Ye Qinghua, Zhang Shuhong, Yang Runshi, Zhao Hui, Wu Lei, Liang Tingting, Xie Xinqiang, Wu Qingping
School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China.
Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China.
Foods. 2022 Aug 4;11(15):2332. doi: 10.3390/foods11152332.
Probiotic fermented milk can lower the incidence rate of hypertension and is beneficial to the regulation of the intestinal microecology. However, the underlying molecular mechanism remains elusive. Here, we evaluated the role of the gut microbiota and its metabolites in the antihypertensive effect of milk fermented by the Lactiplantibacillus plantarum strains SR37-3 (PFM-SR37-3) and SR61-2 (PFM-SR61-2) in Ng-nitro-L-arginine methyl ester induced hypertensive rats. The results showed that PFM-SR37-3 and PFM-SR61-2 intervention significantly lowered the blood pressure (BP) of NG-nitro-L-arginine methyl ester induced hypertensive rats and attenuated renal injury. In particular, long-term administration of PFM inhibited a progressive elevation in SBP (170.22 ± 8.40 and 133.28 ± 6.09 by model group and PFM-SR37-3 treated model group, respectively, at the end of the 4 weeks; p < 0.01 PFM-SR37-3 treated model group versus model group) and DBP (133.83 ± 5.91 and 103.00 ± 6.41 by model group and PFM-SR37-3 treated model group, respectively, at the end of the 4 weeks; p < 0.01 PFM-SR37-3 treated model group versus model group). PFM-SR37-3 and PFM-SR61-2 reshaped the gut microbiome and metabolome, and especially regulated the metabolic levels of L-phenylalanine, L-methionine and L-valine in the intestine and blood circulation. The analysis of the target organ’s aortic transcriptome indicated that the protective effects of PFM-SR37-3 and PFM-SR61-2 were accompanied by the modulation of the BP circadian rhythm pathway, which was conducive to cardiovascular function. Vascular transcriptomic analysis showed that circadian rhythm and AMPK might be potential targets of hypertension. In addition, the ACE inhibition rates of Lactiplantibacillus plantarum SR37-3 and Lactiplantibacillus plantarum SR61-2 in vitro were 70.5% and 68.9%, respectively. Our research provides new insights into novel and safe options for hypertension treatment.
益生菌发酵乳可降低高血压发病率，有利于肠道微生态的调节。然而，其潜在的分子机制仍不清楚。在此，我们评估了肠道微生物群及其代谢产物在植物乳杆菌SR37-3（PFM-SR37-3）和SR61-2（PFM-SR61-2）发酵乳对N-硝基-L-精氨酸甲酯诱导的高血压大鼠的降压作用中的作用。结果表明，PFM-SR37-3和PFM-SR61-2干预显著降低了N-硝基-L-精氨酸甲酯诱导的高血压大鼠的血压（BP），并减轻了肾损伤。特别是，长期给予PFM可抑制收缩压的逐渐升高（4周结束时，模型组为170.22±8.40，PFM-SR37-3治疗模型组为133.28±6.09；PFM-SR37-3治疗模型组与模型组相比，p<0.01）和舒张压（4周结束时，模型组为133.83±5.91，PFM-SR37-3治疗模型组为103.00±6.41；PFM-SR37-3治疗模型组与模型组相比，p<0.01）。PFM-SR37-3和PFM-SR61-2重塑了肠道微生物组和代谢组，尤其调节了肠道和血液循环中L-苯丙氨酸、L-蛋氨酸和L-缬氨酸的代谢水平。对靶器官主动脉转录组的分析表明，PFM-SR37-3和PFM-SR61-2的保护作用伴随着血压昼夜节律途径的调节，这有利于心血管功能。血管转录组分析表明，昼夜节律和AMPK可能是高血压的潜在靶点。此外，植物乳杆菌SR37-3和植物乳杆菌SR61-2在体外的ACE抑制率分别为70.5%和68.9%。我们的研究为高血压治疗的新的安全选择提供了新的见解。
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