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

<b>Introduction.</b> Hypertension is the most prevalent chronic disease and a major risk factor for cardiovascular and cerebrovascular diseases.<b>Gap statement.</b> However, there has been no substantial breakthrough in aetiology, new drug targets, and drug development of hypertension in recent 50 years.<b>Research aim.</b> 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.<b>Methods.</b> 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.<b>Results.</b> The composition of gut microbiota in patients exhibited dissimilarities compared to that in healthy subjects, which was distinguished by <i>Prevotella, Slackia</i>, <i>Enterococcus</i>, <i>Bifidobacterium,</i> and <i>Lactobacillales</i> may be potential markers for tracking the progression of hypertension, and <i>Bifidobacterium</i>, <i>Butyricimonas</i>, <i>Adlercreutzia</i>, <i>Faecalibacterium</i>, <i>Lactobacillus</i>, <i>Ruminococcus</i>, <i>Clostridium</i>, and <i>Acidaminococcus</i> 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 <i>Bifidobacterium</i> 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, <i>Coprococcus</i> may cause changes in albumin through the influence of androsterone enanthate.<b>Conclusions.</b> 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.