Table2_A cross-sectional study identifying disparities in serum metabolic profiles among hypertensive patients with ISH, IDH and SDH subtypes.doc

BackgroundIt has been well acknowledged that disordered intestinal microflora and their fermented products play crucial role during the development of hypertension (HTN). Aberrant profiles of fecal bacteria have been documented in subjects with isolated systolic HTN (ISH) and isolated diastolic HTN (IDH) previously. Nevertheless, evidence regarding the association of metabolic products in the bloodstream with ISH, IDH and combined systolic and diastolic HTN (SDH) remains scarce.
MethodsWe performed a cross-sectional study and conducted untargeted liquid chromatography-mass spectrometry (LC/MS) analysis on serum samples of 119 participants, including 13 subjects with normotension (SBP < 120/DBP < 80 mm Hg), 11 individuals with ISH (SBP ≥ 130/DBP < 80 mm Hg), 27 patients with IDH (SBP < 130/DBP ≥ 80 mm Hg), and 68 SDH patients (SBP ≥ 130, DBP ≥ 80 mm Hg).
ResultsHere, the results showed clearly separated clusters in PLS-DA and OPLS-DA score plots for patients suffering from ISH, IDH and SDH when compared with normotension controls. The ISH group was characterized by elevated levels of 3,5-tetradecadien carnitine and notable reduction of maleic acid. While IDH patients were enriched with metabolites in L-lactic acid and depleted in citric acid. Stearoylcarnitine was identified to be specifically enriched in SDH group. The differentially abundant metabolites between ISH and controls were involved in tyrosine metabolism pathways, and in biosynthesis of phenylalanine for those between SDH and controls. Potential linkages between the gut microbial and serum metabolic signatures were detected within ISH, IDH and SDH groups. Furthermore, we found the association of discriminatory metabolites with the characteristics of patients.
ConclusionOur findings demonstrate disparate blood metabolomics signatures across ISH, IDH and SDH, with differentially enriched metabolites and potential functional pathways identified, reveal the underlying microbiome and metabolome network in HTN subtypes, and provide potential targets for disease classification and therapeutic strategy in clinical practice.

背景 目前学界已普遍认可，肠道菌群紊乱及其发酵产物在高血压（hypertension, HTN）的发生发展中发挥关键作用。既往研究已证实，单纯收缩期高血压（isolated systolic HTN, ISH）与单纯舒张期高血压（isolated diastolic HTN, IDH）患者的粪便菌群谱存在异常。然而，针对血液循环代谢产物与ISH、IDH及收缩舒张联合性高血压（combined systolic and diastolic HTN, SDH）之间关联的研究证据仍较为匮乏。
方法 本研究开展了一项横断面研究，对119名受试者的血清样本进行非靶向液相色谱-质谱联用（liquid chromatography-mass spectrometry, LC/MS）分析。受试者涵盖13名血压正常者（收缩压<120mmHg且舒张压<80mmHg）、11名ISH患者（收缩压≥130mmHg且舒张压<80mmHg）、27名IDH患者（收缩压<130mmHg且舒张压≥80mmHg）以及68名SDH患者（收缩压≥130mmHg且舒张压≥80mmHg）。
结果 本研究结果显示，在偏最小二乘判别分析（PLS-DA）与正交偏最小二乘判别分析（OPLS-DA）得分图中，ISH、IDH及SDH患者与血压正常对照者可被清晰区分为不同聚类簇。ISH组以3,5-十四碳烯肉碱水平升高及马来酸水平显著降低为特征。IDH患者的血清中L-乳酸代谢物富集，而柠檬酸水平则出现耗竭。硬脂酰肉碱被鉴定为SDH组特有的富集代谢物。ISH组与对照组的差异丰度代谢物参与酪氨酸代谢通路，SDH组与对照组的差异丰度代谢物则涉及苯丙氨酸生物合成通路。在ISH、IDH及SDH各组中，均检测到肠道菌群特征与血清代谢组特征之间存在潜在关联。此外，本研究还发现差异判别代谢物与患者临床特征存在相关性。
结论 本研究结果表明，ISH、IDH与SDH这三种高血压亚型的血液代谢组特征存在显著差异，本研究鉴定出了差异富集的代谢物及潜在功能通路，揭示了高血压亚型中潜在的菌群-代谢组调控网络，并为临床疾病分类与治疗策略开发提供了潜在靶点。