Centre for Nutrition Education and Lifestyle Management, Chapel Gardens, 14 Rectory Road, Wokingham RG40 1DH, England, United Kingdom.
Centre for Nutrition Education and Lifestyle Management, Chapel Gardens, 14 Rectory Road, Wokingham RG40 1DH, England, United Kingdom.
Biomed Pharmacother. 2021 May;137:111334. doi: 10.1016/j.biopha.2021.111334. Epub 2021 Feb 5.
High blood pressure (BP) presents a significant public health challenge. Recent findings suggest that altered microbiota can exert a hypertensive effect on the host. One of the possible mechanisms involved is the chronic translocation of its components, mainly lipopolysaccharides (LPS) into systemic circulation leading to metabolic endotoxemia. In animal models, LPS has been commonly used to induce endothelial dysfunction and vascular inflammation. In human studies, plasma LPS concentration has been positively correlated with hypertension, however, the mechanistic link has not been fully elucidated. It is hypothesised here that the LPS-induced direct alterations to the vascular endothelium and resulting hypertension are possible targets for probiotic intervention. The methodology of this review involved a systematic search of the literature with critical appraisal of papers. Three tranches of search were performed: 1) existing review papers; 2) primary mechanistic animal, in vitro and human studies; and 3) primary intervention studies. A total of 70 peer-reviewed papers were included across the three tranches and critically appraised using SIGN50 for human studies and the ARRIVE guidelines for animal studies. The extracted information was coded into key themes and summarized in a narrative analysis. Results highlight the role of LPS in the activation of endothelial toll-like receptor 4 (TLR4) initiating a cascade of interrelated signalling pathways including: 1) Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase/ Reactive oxygen species (ROS)/ Endothelial nitric oxide synthase (eNOS) pathway leading to endothelial dysfunction; and 2) Mitogen-Activated Protein Kinase (MAPK) and Nuclear factor kappa B (NF-κB) pathways leading to vascular inflammation. Findings from animal intervention studies suggest an improvement in vasorelaxation, vascular inflammation and hypertension following probiotic supplementation, which was mediated by downregulation of LPS-induced pathways. Randomised controlled trials (RCTs) and systematic reviews provided some evidence for the anti-inflammatory effect of probiotics with statistically significant antihypertensive effect in clinical samples and may offer a viable intervention for the management of hypertension.
高血压（BP）是一个重大的公共健康挑战。最近的研究结果表明，改变的微生物群落可能对宿主产生高血压效应。其中一个可能的机制是其成分的慢性易位，主要是脂多糖（LPS）进入全身循环，导致代谢性内毒素血症。在动物模型中，LPS 通常被用于诱导内皮功能障碍和血管炎症。在人类研究中，血浆 LPS 浓度与高血压呈正相关，然而，其机制联系尚未完全阐明。这里假设 LPS 诱导的血管内皮直接改变和由此导致的高血压可能是益生菌干预的靶点。本综述的方法学涉及对文献进行系统搜索和对论文进行批判性评估。进行了三批搜索：1）现有综述论文；2）主要的机制性动物、体外和人类研究；3）主要的干预研究。总共在这三批中纳入了 70 篇同行评议论文，并使用 SIGN50 对人类研究和 ARRIVE 指南对动物研究进行了批判性评估。提取的信息被编码为关键主题，并以叙述性分析进行总结。结果强调了 LPS 在激活内皮 Toll 样受体 4（TLR4）中的作用，启动了一系列相互关联的信号通路，包括：1）烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶/活性氧（ROS）/内皮型一氧化氮合酶（eNOS）途径导致内皮功能障碍；和 2）丝裂原激活蛋白激酶（MAPK）和核因子 kappa B（NF-κB）途径导致血管炎症。动物干预研究的结果表明，益生菌补充后血管舒张、血管炎症和高血压得到改善，这是通过下调 LPS 诱导的途径介导的。随机对照试验（RCT）和系统评价提供了一些益生菌抗炎作用的证据，在临床样本中具有统计学显著的降压作用，可能为高血压的管理提供一种可行的干预措施。
