Department of Biochemistry & Molecular Biology, University of Florida, Gainesville, FL 32610, United States.
Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, United States.
Int J Cardiol. 2018 Nov 15;271:336-339. doi: 10.1016/j.ijcard.2018.04.074. Epub 2018 Jul 23.
Black Americans have greater rates, severity and resistance to treatment of hypertension than White Americans. The gut microbiota and its metabolites may contribute to this. This concept was tested in a pilot study.
Subjects with high (HBP, >140/80 mm Hg) and normal (NBP, <120/80 mm Hg) blood pressure (BP) provided stool and blood samples for whole genome sequencing (WGS) of gut microbiota and global untargeted metabolomics of serum. Patients were either black (B) with NBP (n = 10 for WGS, 5 for metabolomics) and HBP (n = 10 and 9, BHBP) or white (W) with NBP (n = 20 and 13, WNBP) and HBP (n = 12 and 8, WHBP).
All four subject groups had distinct gut microbiota taxonomy by partial least squares discriminant analysis (PLS-DA). More importantly, linear discriminant analysis effect size showed marked differences in function of the microbiota of BHBP and WHBP (PLS-DA) with LDA scores <1. This included pathways for synthesis and interconversion of amino acids and inflammatory antigens. Similarly, metabolites differed (PLS-DA) with BHBP having significantly higher sulfacetaldehyde, quinolinic acid, 5-aminolevulinic acid, leucine and phenylalanine and lower 4-oxoproline and l-anserine.
Combination analyses of functional gut metabolic pathways and metabolomics data in this small pilot study suggest that BHBP may have greater oxidative stress markers in plasma, greater inflammatory potential of the gut microbiome and altered metabolites with gut microbial functions implying insulin resistance. A fuller understanding of these potential differences could lead to race-based treatments for hypertension.
黑种美国人高血压的发病率、严重程度和治疗抵抗率均高于白种美国人。肠道微生物群及其代谢产物可能对此有一定影响。本研究旨在通过一项初步研究验证这一假说。
本研究纳入了血压正常(<120/80mmHg)和高血压(>140/80mmHg)的受试者,收集其粪便和血液样本,用于肠道微生物组的全基因组测序(WGS)和血清的非靶向代谢组学分析。受试者的种族分为黑人(B)和白人(W),血压状态分为正常(NBP)和高血压(HBP)。
偏最小二乘判别分析(PLS-DA)显示,所有四组受试者的肠道微生物群分类学均存在差异。更重要的是,线性判别分析效应大小(LDA)显示,BHBP 和 WHBP 的肠道微生物群功能存在显著差异(PLS-DA,LDA 评分<1),包括氨基酸和炎症抗原的合成和相互转化途径。同样,代谢物也存在差异(PLS-DA),BHBP 中硫代乙醛酸、喹啉酸、5-氨基乙酰丙酸、亮氨酸和苯丙氨酸的水平显著升高,而 4-氧脯氨酸和 l-肌氨酸的水平显著降低。
本初步研究中,对肠道代谢功能途径的组合分析和代谢组学数据的分析结果提示,BHBP 可能具有更高的血浆氧化应激标志物、肠道微生物群的更高炎症潜能以及肠道微生物功能相关的代谢物改变,这些改变可能与胰岛素抵抗有关。进一步深入了解这些潜在差异,可能会为基于种族的高血压治疗提供新的思路。