Ozbek Deniz Aral, Koc Neriman Sila, İnal Nese, Kablan Sevilay Erdogan, Kaygusuz Yunus, Karahan Sevilay, Uyaroğlu Oğuz Abdullah, Yildirim Tolga, Ergunay Koray, Nemutlu Emirhan, Akyon Yakut, Altun Bulent
Hacettepe University Faculty of Medicine, Department of Nephrology.
Hacettepe University Faculty of Medicine, Department of Medical Microbiology.
J Hypertens. 2025 Sep 1;43(9):1539-1553. doi: 10.1097/HJH.0000000000004086. Epub 2025 Jun 23.
Accumulating evidence has shown an association between stool microbiome and hypertension. However, gut microbiome and metabolome of nondipping blood pressure (BP), high BP variability and morning BP surge have not been extensively studied. Here, we aimed to investigate the interplay between the gut microbiome, metabolome and 24-h urine sodium (Na) levels in different BP phenotypes.
This study included 45 newly diagnosed hypertensive, and healthy participants. Ambulatory BP monitoring was performed in all patients to confirm the diagnosis and determine corresponding BP phenotypes. Gut microbiome and metabolome were determined using 16S ribosomal RNA sequencing and gas chromatography-mass spectrometry, respectively.
Firmicutes / Bacteroides ratio was higher in nondipper than dipper group ( P = 0.01). Comparative analyses showed that 23 species, 21 genera and 9 families were significantly differentiated in different BP phenotype subgroups. Functional metabolomic enrichment analysis of nondipper patients showed enrichment of catecholamine biosynthesis and tyrosine metabolism due to noradrenaline, dopamine, 3,4-dihydroxyphenylglycol and 3,4-dihydroxyphenylacetic acid. Spearman analyses between significantly enriched metabolites and organized taxonomic units (OTUs) in nondipper patients showed correlations between 3,4-dihydroxyphenylglycol and Parabacteroides diastonis (rho = -0.33, P = 0.03) and dopamine with Chryseobacterium genus (rho = 0.71, P = 0.02). Enterococcus, Lachnobacterium, Odoribacter and Pseudomonas were positively, whereas Lactobacillus and Clostridium were negatively correlated with urine Na levels.
We revealed novel relationships among gut microbiome, metabolome and sodium intake in different BP phenotypes. Enrichment of catecholamine synthesis and correlations between OTUs and metabolites in nondipper patients indicated that sympathetic system activation via gut-brain axis could play a role in the nondipping BP profile.
越来越多的证据表明粪便微生物群与高血压之间存在关联。然而,非勺型血压(BP)、高BP变异性和晨起血压激增的肠道微生物群和代谢组尚未得到广泛研究。在此,我们旨在研究不同BP表型中肠道微生物群、代谢组和24小时尿钠(Na)水平之间的相互作用。
本研究纳入了45名新诊断的高血压患者和健康参与者。对所有患者进行动态血压监测以确诊并确定相应的BP表型。分别使用16S核糖体RNA测序和气相色谱-质谱法测定肠道微生物群和代谢组。
非勺型组的厚壁菌门/拟杆菌门比率高于勺型组(P = 0.01)。比较分析表明,23个物种、21个属和9个科在不同BP表型亚组中存在显著差异。对非勺型患者的功能代谢组富集分析显示,由于去甲肾上腺素、多巴胺、3,4-二羟基苯乙二醇和3,4-二羟基苯乙酸,儿茶酚胺生物合成和酪氨酸代谢得到富集。非勺型患者中显著富集的代谢物与分类学单位(OTU)之间的Spearman分析显示,3,4-二羟基苯乙二醇与迟缓副拟杆菌之间存在相关性(rho = -0.33,P = 0.03),多巴胺与金黄杆菌属之间存在相关性(rho = 0.71,P = 0.02)。肠球菌、乳酸杆菌、气味杆菌和假单胞菌与尿钠水平呈正相关,而乳酸杆菌和梭菌与尿钠水平呈负相关。
我们揭示了不同BP表型中肠道微生物群、代谢组和钠摄入之间的新关系。非勺型患者中儿茶酚胺合成的富集以及OTU与代谢物之间的相关性表明,通过肠-脑轴激活交感神经系统可能在非勺型BP模式中起作用。