Alterations of the Gut Microbiome in Hypertension.

Alterations of the Gut Microbiome in Hypertension.
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高血压患者肠道微生物组的改变

DOI:
10.3389/fcimb.2017.00381
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发表时间:
2017
影响因子:
5.7
通讯作者:
Ma Y
Ma Y
中科院分区:
医学2区
文献类型:
--
作者:
Yan Q;Gu Y;Li X;Yang W;Jia L;Chen C;Han X;Huang Y;Zhao L;Li P;Fang Z;Zhou J;Guan X;Ding Y;Wang S;Khan M;Xin Y;Li S;Ma Y

文献摘要

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人类肠道微生物群被认为直接或间接参与心血管疾病和高血压。然而,高血压相关肠道微生物的鉴定和功能状态尚未得到全面调查。研究方法: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的粪便样本,基于全宏基因组鸟枪测序,对高血压状态下的肠道微生物组进行了表征。结果:高血压导致肠道菌群失调,样品内多样性显著降低,微生物组成发生变化。宏基因组关联研究(MGWAS)揭示了53,953个微生物基因在患者和健康对照之间的分布不同(错误发现率,0.05),并可分为68个代表细菌物种的簇。病原体分类群,如克雷伯氏菌属,链球菌属,和Parabacteroides merdae经常分布在高血压肠道微生物组中,而短链脂肪酸生产者,如Roseburia spp.和Faecalibacterium prausnitzii在对照组中较高。高血压相关物种的数量与疾病的严重程度也有较强的相关性。在功能上,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,发现氨基酸、辅因子和维生素的代谢更高。我们进一步提供了用于疾病区分的微生物标志物,并实现了0.78的受试者工作特征曲线下面积(AUC),证明了肠道微生物群在预测高血压方面的潜力。结论:这些发现代表了高血压肠道微生物组的微生物多样性、基因、物种和功能的特定改变。深入研究高血压与肠道菌群之间的因果关系,将为高血压及其相关疾病的治疗和预防提供新的前景。
Introduction: 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. Methods: 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. Results: 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, Klebsiella spp., Streptococcus spp., and Parabacteroides merdae were frequently distributed in hypertensive gut microbiome, whereas the short-chain fatty acid producer, such as, Roseburia spp. and Faecalibacterium prausnitzii, 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. Conclusion: 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.