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高血压患者的肠道微生物组改变。

Alterations of the Gut Microbiome in Hypertension.

机构信息

Department of Biochemistry and Molecular Biology, Dalian Medical UniversityDalian, China.

Department of Microbiology, Dalian Medical UniversityDalian, China.

出版信息

Front Cell Infect Microbiol. 2017 Aug 24;7:381. doi: 10.3389/fcimb.2017.00381. eCollection 2017.

Abstract

Human gut microbiota is believed to be directly or indirectly involved in cardiovascular diseases and hypertension. However, the identification and functional status of the hypertension-related gut microbe(s) have not yet been surveyed in a comprehensive manner. Here we characterized the gut microbiome in hypertension status by comparing fecal samples of 60 patients with primary hypertension and 60 gender-, age-, and body weight-matched healthy controls based on whole-metagenome shotgun sequencing. Hypertension implicated a remarkable gut dysbiosis with significant reduction in within-sample diversity and shift in microbial composition. Metagenome-wide association study (MGWAS) revealed 53,953 microbial genes that differ in distribution between the patients and healthy controls (false discovery rate, 0.05) and can be grouped into 68 clusters representing bacterial species. Opportunistic pathogenic taxa, such as, spp., spp., and were frequently distributed in hypertensive gut microbiome, whereas the short-chain fatty acid producer, such as, spp. and , were higher in controls. The number of hypertension-associated species also showed stronger correlation to the severity of disease. Functionally, the hypertensive gut microbiome exhibited higher membrane transport, lipopolysaccharide biosynthesis and steroid degradation, while in controls the metabolism of amino acid, cofactors and vitamins was found to be higher. We further provided the microbial markers for disease discrimination and achieved an area under the receiver operator characteristic curve (AUC) of 0.78, demonstrating the potential of gut microbiota in prediction of hypertension. These findings represent specific alterations in microbial diversity, genes, species and functions of the hypertensive gut microbiome. Further studies on the causality relationship between hypertension and gut microbiota will offer new prospects for treating and preventing the hypertension and its associated diseases.

摘要

人类肠道微生物群被认为直接或间接地参与了心血管疾病和高血压的发生。然而,高血压相关的肠道微生物(群)的鉴定和功能状态尚未得到全面调查。在这里,我们通过比较 60 名原发性高血压患者和 60 名性别、年龄和体重匹配的健康对照者的粪便样本,基于全宏基因组鸟枪法测序,描述了高血压状态下的肠道微生物组。高血压显著影响肠道微生物失调,样本内多样性显著降低,微生物组成发生变化。全宏基因组关联研究(MGWAS)显示,在患者和健康对照组之间分布差异显著的微生物基因有 53953 个(错误发现率,0.05),可分为 68 个聚类,代表细菌种。机会性病原体,如 spp.、 spp. 和 spp.,在高血压肠道微生物组中频繁分布,而短链脂肪酸产生菌,如 spp. 和 spp.,在对照组中较高。与高血压相关的物种数量也与疾病的严重程度有更强的相关性。功能上,高血压肠道微生物组表现出更高的膜转运、脂多糖生物合成和类固醇降解,而在对照组中,氨基酸、辅因子和维生素的代谢更高。我们进一步提供了疾病区分的微生物标志物,实现了 0.78 的接收者操作特征曲线(ROC)下面积(AUC),表明肠道微生物群在预测高血压方面具有潜力。这些发现代表了高血压肠道微生物组中微生物多样性、基因、物种和功能的特定变化。进一步研究高血压与肠道微生物之间的因果关系将为治疗和预防高血压及其相关疾病提供新的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d8a/5573791/c98ada6969d2/fcimb-07-00381-g0001.jpg

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