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中国成年人血压与肠道微生物群和宿主血浆代谢物的关联。

Gut Microbiota and Host Plasma Metabolites in Association with Blood Pressure in Chinese Adults.

机构信息

From the Department of Nutrition (Y.W., M.C.B.T., K.A.M., P.G.-L.), University of North Carolina at Chapel Hill (UNC-Chapel Hill).

National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing (H.W., J.Z., CS., Z.W., B.Z.).

出版信息

Hypertension. 2021 Feb;77(2):706-717. doi: 10.1161/HYPERTENSIONAHA.120.16154. Epub 2020 Dec 21.

Abstract

Animal studies have revealed gut microbial and metabolic pathways of blood pressure (BP) regulation, yet few epidemiological studies have collected microbiota and metabolomics data in the same individuals. In a population-based, Chinese cohort who did not report antihypertension medication use (30-69 years, 54% women), thus minimizing BP treatment effects, we examined multivariable-adjusted (eg, diet, physical activity, smoking, kidney function), cross-sectional associations between measures of gut microbiota (16S rRNA [ribosomal ribonucleic acid], N=1003), and plasma metabolome (liquid chromatography-mass spectrometry, N=434) with systolic (SBP, mean [SD]=126.0 [17.4] mm Hg) and diastolic BP (DBP [80.7 (10.7) mm Hg]). We found that the overall microbial community assessed by principal coordinate analysis varied by SBP and DBP (permutational multivariate ANOVA <0.05). To account for strong correlations across metabolites, we first examined metabolite patterns derived from principal component analysis and found that a lipid pattern was positively associated with SBP (linear regression coefficient [95% CI] per 1 SD pattern score: 2.23 [0.72-3.74] mm Hg) and DBP (1.72 [0.81-2.63] mm Hg). Among 1104 individual metabolites, 34 and 39 metabolites were positively associated with SBP and DBP (false discovery rate-adjusted linear model <0.05), respectively, including linoleate, palmitate, dihomolinolenate, 8 sphingomyelins, 4 acyl-carnitines, and 2 phosphatidylinositols. Subsequent pathway analysis showed that metabolic pathways of long-chain saturated acylcarnitine, phosphatidylinositol, and sphingomyelins were associated with SBP and DBP (false discovery rate-adjusted Fisher exact test <0.05). Our results suggest potential roles of microbiota and metabolites in BP regulation to be followed up in prospective and clinical studies.

摘要

动物研究揭示了肠道微生物和血压(BP)调节的代谢途径,但很少有流行病学研究在同一人群中同时收集微生物组和代谢组学数据。在一个基于人群的、未报告使用抗高血压药物的中国队列中(30-69 岁,女性占 54%),因此最小化了 BP 治疗效果,我们检查了肠道微生物组(16S rRNA[核糖体 RNA],N=1003)和血浆代谢组(液相色谱-质谱法,N=434)与收缩压(SBP,平均值[标准差]=126.0[17.4]mmHg)和舒张压(DBP[80.7[10.7]mmHg])之间的多变量调整(例如,饮食、体力活动、吸烟、肾功能)的横断面关联。我们发现,通过主坐标分析评估的整体微生物群落因 SBP 和 DBP 而有所不同(置换多元方差分析<0.05)。为了考虑代谢物之间的强相关性,我们首先检查了主成分分析得出的代谢物模式,发现脂质模式与 SBP 呈正相关(线性回归系数[95%CI]每 1 个标准差模式得分:2.23[0.72-3.74]mmHg)和 DBP(1.72[0.81-2.63]mmHg)。在 1104 种单个代谢物中,有 34 种和 39 种代谢物与 SBP 和 DBP 呈正相关(经错误发现率调整的线性模型<0.05),包括亚油酸、棕榈酸、二同型亚麻酸、8 种神经鞘磷脂、4 种酰基辅酶 A 和 2 种磷脂酰肌醇。随后的途径分析表明,长链饱和酰基辅酶 A、磷脂酰肌醇和神经鞘磷脂的代谢途径与 SBP 和 DBP 相关(经错误发现率调整的 Fisher 精确检验<0.05)。我们的结果表明,肠道微生物组和代谢物在 BP 调节中的潜在作用有待前瞻性和临床研究进一步验证。

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