Unique intestinal microflora and metabolic profile in different stages of hypertension reveal potential biomarkers for early diagnosis and prognosis.

Yaren Yu, Jiayi Zhu, Ruixue Fu, Lina Guo, Tao Chen, Zhaoyan Xu, Jianyu Zhang, Wensheng Chen, Lushi Chen, Xili Yang
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Abstract

Introduction. Hypertension is the most prevalent chronic disease and a major risk factor for cardiovascular and cerebrovascular diseases.Gap statement. However, there has been no substantial breakthrough in aetiology, new drug targets, and drug development of hypertension in recent 50 years.Research aim. Therefore, this study was to screen unique intestinal microbiome and serum metabolic biomarkers which can early diagnose and track the prognosis of hypertension patients in different periods, and analyse its underlying mechanisms and functions.Methods. Four groups of stool and serum samples, including healthy controls (HCs), prehypertension (PHT), hypertension (HT), and hypertension-related complications (HTC), were collected. Microbial diversity assessed using 16S rRNA sequencing. The metabolites in serum samples were detected through LC-MS/MS analysis.Results. The composition of gut microbiota in patients exhibited dissimilarities compared to that in healthy subjects, which was distinguished by Prevotella, Slackia, Enterococcus, Bifidobacterium, and Lactobacillales may be potential markers for tracking the progression of hypertension, and Bifidobacterium, Butyricimonas, Adlercreutzia, Faecalibacterium, Lactobacillus, Ruminococcus, Clostridium, and Acidaminococcus demonstrated diagnostic value. Meanwhile, tracking the dynamic changes of deoxycholic acid, 4-oxododecanedioic acid, and l-arginine can serve as biomarkers for early diagnosis, and investigation into the mechanism by which the intestinal microbiome influences the onset and progression of hypertension. In terms of pathogenesis, the findings revealed that Bifidobacterium may caused the changes of AST, indirect bilirubin, ALT, triglyceride and uric acid by affecting metabolites cis-7-hexadecenoic acid methyl ester and N1-acetylspermidine. Additionally, Coprococcus may cause changes in albumin through the influence of androsterone enanthate.Conclusions. These findings highlight that the unique intestinal microbiome and serum metabolic profile in different periods of hypertension will provide valuable insight for timely diagnosis and prognosis tracking in hypertension patients with promising clinical applications.

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不同阶段高血压患者独特的肠道微生物菌群和代谢特征揭示了早期诊断和预后的潜在生物标志物。
导言。高血压是发病率最高的慢性疾病,也是心脑血管疾病的主要危险因素。然而,近 50 年来,高血压的病因学、新药靶点和药物开发方面一直没有实质性突破。因此,本研究旨在筛选可早期诊断和追踪不同时期高血压患者预后的独特肠道微生物组和血清代谢生物标志物,并分析其潜在机制和功能。收集了四组粪便和血清样本,包括健康对照组(HCs)、高血压前期(PHT)、高血压(HT)和高血压相关并发症(HTC)。使用 16S rRNA 测序评估微生物多样性。通过 LC-MS/MS 分析检测血清样本中的代谢物。与健康受试者相比,患者肠道微生物群的组成表现出差异,其中普雷沃特氏菌、斯拉克氏菌、肠球菌、双歧杆菌和乳酸杆菌可能是追踪高血压进展的潜在标记物,而双歧杆菌、丁酸杆菌、阿德勒克鲁兹氏菌、粪杆菌、乳酸杆菌、反刍球菌、梭菌和酸氨球菌则具有诊断价值。同时,跟踪脱氧胆酸、4-氧代十二烷二酸和精氨酸的动态变化可作为早期诊断的生物标志物,并研究肠道微生物组影响高血压发病和进展的机制。在发病机制方面,研究结果显示,双歧杆菌可通过影响代谢产物顺式-7-十六碳烯酸甲酯和 N1-乙酰基过氨酸,引起 AST、间接胆红素、ALT、甘油三酯和尿酸的变化。此外,科普洛球菌还可能通过庚酸雄酮的影响导致白蛋白发生变化。这些研究结果表明,不同时期高血压患者独特的肠道微生物组和血清代谢谱将为高血压患者的及时诊断和预后跟踪提供有价值的见解,具有广阔的临床应用前景。
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