School of Biological Science and Technology, College of Science and Engineering, Kanazawa University, Kanazawa, Japan.
Institute of Liberal Arts and Science, Kanazawa University, Kanazawa, Japan.
Hypertens Res. 2023 Oct;46(10):2280-2292. doi: 10.1038/s41440-023-01334-7. Epub 2023 Jun 6.
The renin-angiotensin-aldosterone system (RAAS) is a regulatory mechanism of the endocrine system and is associated with various diseases, including hypertension and renal and cardiovascular diseases. The gut microbiota (GM) have been associated with various diseases, mainly in animal models. However, to our knowledge, no studies have examined the relationship between the RAAS and GM in humans. The present study aimed to assess the association between the systemic RAAS and GM genera and their causal relationships. The study participants were 377 members of the general population aged 40 years or older in Shika-machi, Japan. Plasma renin activity (PRA), plasma aldosterone concentration (PAC), aldosterone-renin ratio (ARR), and GM composition were analyzed using the 16S rRNA method. The participants were divided into high and low groups according to the PRA, PAC, and ARR values. U-tests, one-way analysis of covariance, and linear discriminant analysis of effect size were used to identify the important bacterial genera between the two groups, and binary classification modeling using Random Forest was used to calculate the importance of the features. The results showed that Blautia, Bacteroides, Akkermansia, and Bifidobacterium were associated with the RAAS parameters. Causal inference analysis using the linear non-Gaussian acyclic model revealed a causal effect of Blautia on PAC via SBP. These results strengthen the association between the systemic RAAS and GM in humans, and interventions targeting the GM may provide new preventive measures and treatments for hypertension and renal disease.
肾素-血管紧张素-醛固酮系统（RAAS）是内分泌系统的调节机制，与各种疾病有关，包括高血压、肾脏和心血管疾病。肠道微生物群（GM）与各种疾病有关，主要在动物模型中。然而，据我们所知，没有研究检查过 RAAS 和 GM 在人类中的关系。本研究旨在评估系统 RAAS 和 GM 属之间的关联及其因果关系。研究参与者是日本志贺町年龄在 40 岁或以上的 377 名普通人群。使用 16S rRNA 方法分析血浆肾素活性（PRA）、血浆醛固酮浓度（PAC）、醛固酮-肾素比（ARR）和 GM 组成。根据 PRA、PAC 和 ARR 值，将参与者分为高和低两组。使用 U 检验、单向方差分析和效应大小的线性判别分析来识别两组之间重要的细菌属，使用随机森林进行二元分类建模来计算特征的重要性。结果表明，Blautia、Bacteroides、Akkermansia 和 Bifidobacterium 与 RAAS 参数有关。使用线性非高斯非循环模型进行因果推理分析表明，Blautia 通过 SBP 对 PAC 有因果影响。这些结果加强了人类系统 RAAS 和 GM 之间的关联，针对 GM 的干预可能为高血压和肾脏疾病提供新的预防措施和治疗方法。
