JOURNAL OF HYPERTENSION, vol.43, no.9, pp.1539-1553, 2025 (SCI-Expanded)
Objective: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.Methods: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.Results: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.Conclusion: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.