高血压患者的肠道菌群失调且肠道屏蔽功能存在障碍
Title：
Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure
Abstract：
Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models. However, whether this association exists in humans is unknown. Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP). Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects. Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability. Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP. Zonulin strongly correlated with SBP (R= 0.5301,<0.0001). Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R= 0.4608,<0.0001). The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP. These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans. They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN.
All Authors：
Seungbum Kim,Ruby Goel,Ashok Kumar,Yanfei Qi,Gil Lobaton,Koji Hosaka,Mohammed Mohammed,Eileen M Handberg,Elaine M Richards,Carl J Pepine,Mohan K Raizada
First Authors：
Seungbum Kim
Correspondence：
Carl J Pepine,Mohan K Raizada
摘要：
通过对22名高血压患者及18名血压正常的健康人进行对比分析发现： 高血压患者的粪便菌群组成及功能发生显著变化，粪便中丁酸盐的含量也显著降低，较多的产丁酸菌与较低的收缩压相关；高血压患者的血清中，肠道脂肪酸结合蛋白（I-FABP）、LPS、Th17细胞增加，说明肠道炎症及肠道通透性有升高，其中连蛋白（肠道上皮紧密连接蛋白调节因子）的显著升高进一步显示高血压患者的肠道屏障功能障碍，而连蛋白与收缩压显著相关。