Department of Pharmacology, School of Pharmacy and Center for Biomedical Research (CIBM), University of Granada, Granada, Spain.
Gene Regulation in Cardiovascular Remodeling and Inflammation Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
FASEB J. 2020 Oct;34(10):13626-13640. doi: 10.1096/fj.202001532R. Epub 2020 Aug 11.
Many probiotics that affect gut microbial ecology have been shown to produce beneficial effects on renin-angiotensin-dependent rodent models and human hypertension. We hypothesized that Bifidobacterium breve CECT7263 (BFM) would attenuate hypertension in deoxycorticosterone acetate (DOCA)-salt rats, a renin-independent model of hypertension. Rats were randomly divided into five groups: control, DOCA-salt, treated DOCA-salt-BFM, treated DOCA-salt-butyrate, and treated DOCA-salt-acetate, for 5 weeks. BFM prevented the increase in systolic blood pressure, cardiac weight, and renal damage induced by DOCA-salt. BFM increased acetate-producing bacterial population and gut acetate levels, improved colonic integrity, normalized endotoxemia, plasma trimethylamine (TMA) levels, and restored the Th17 and Treg content in mesenteric lymph nodes and aorta. Furthermore, BFM improved nitric oxide-dependent vasorelaxation induced by acetylcholine in aortic rings and reduced NADPH oxidase activity in DOCA-salt animals. These protective effects were mimicked by acetate, but not by butyrate supplementation. These data demonstrate that BFM induces changes in gut microbiota linked with attenuation of endothelial dysfunction and increase in blood pressure in this low-renin form of hypertension. These beneficial effects seem to be mediated by increased acetate and reduced TMA production by gut microbiota, thus, improving gut integrity and restoring Th17/Tregs polarization and endotoxemia.
许多影响肠道微生物生态的益生菌已被证明对肾素-血管紧张素依赖性啮齿动物模型和人类高血压具有有益作用。我们假设短双歧杆菌 CECT7263(BFM)将减轻去氧皮质酮醋酸盐(DOCA)-盐大鼠的高血压,这是一种肾素非依赖性高血压模型。大鼠随机分为五组:对照组、DOCA-盐组、治疗 DOCA-盐-BFM 组、治疗 DOCA-盐-丁酸盐组和治疗 DOCA-盐-醋酸盐组,持续 5 周。BFM 可预防 DOCA-盐引起的收缩压、心脏重量和肾脏损伤增加。BFM 增加了产乙酸菌种群和肠道乙酸水平,改善了结肠完整性,使内毒素血症、血浆三甲胺(TMA)水平正常化,并恢复了肠系膜淋巴结和主动脉中的 Th17 和 Treg 含量。此外,BFM 改善了 DOCA-盐动物中乙酰胆碱诱导的一氧化氮依赖性血管舒张作用,并降低了 NADPH 氧化酶活性。这些保护作用可以被乙酸模拟,但不能被丁酸盐补充模拟。这些数据表明,BFM 诱导肠道微生物群发生变化,与内皮功能障碍的减轻和这种低肾素形式的高血压中的血压升高有关。这些有益作用似乎是通过增加肠道微生物群产生的乙酸和减少 TMA 来介导的,从而改善肠道完整性并恢复 Th17/Tregs 极化和内毒素血症。